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Results for “immune modulation”

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PubMed2004

Epitope DNA vaccines against tuberculosis: spacers and ubiquitin modulates cellular immune responses elicited by epitope DNA vaccine.

Cell-mediated immune responses are crucial in the protection against tuberculosis. In this study, we constructed epitope DNA vaccines (p3-M-38) encoding cytotoxic T lymphocyte (CTL) epitopes of MPT64 and 38 kDa proteins of Mycobacterium tuberculosis. In order to observe the influence of spacer sequence (Ala-Ala-Tyr) or ubiquitin (UbGR) on the efficacy of the two CTL epitopes, we also constructed DNA vaccines, p3-M-S(spacer)-38, p3-Ub (UbGR)-M-S-38 and p3-Ub-M-38. The immune responses elicited by the four DNA vaccines were tested in C57BL/6 (H-2b) mice. The cytotoxicity of T cells was detected by LDH-release method and by enzyme-linked immunospot assay for epitope-specific cells secreting interferon-gamma. The results showed that DNA immunization with p3-M-38 vaccine could induce epitope-specific CD8+ CTL response and that the spacer sequence (AAY) only enhanced M epitope presentation. The protein-targeting sequence (UbGR) enhanced the immunogenicity of the two epitopes. The finding that defined spacer sequences at C-terminus and protein-targeting degradation modulated the immune response of epitope string DNA vaccines will be of importance for the further development of multi-epitope DNA vaccines against tuberculosis.

Animals↗

PubMed1999

Treatment of autoimmune premature ovarian failure.

There is no known immunosuppressive therapy for autoimmune premature ovarian failure that has been proven safe and effective by prospective randomized placebo-controlled study. Nevertheless, immunosuppression using corticosteroids has been used on an empirical basis for this condition. Here we present two cases of young women with premature ovarian failure who were treated with glucocorticoids in the hopes of restoring fertility. The first case illustrates the potential benefit of such therapy, and the second case illustrates a potential risk. The first patient with histologically proven autoimmune oophoritis was treated with alternate day glucocorticoid treatment. She had return of menstrual bleeding six times and ovulatory progesterone concentrations four times over a 16 week period. The second patient with presumed but unconfirmed autoimmune ovarian failure was referred to us after having been treated with a 9 month course of corticosteroids. During that treatment her menses did not resume. The corticosteroid treatment was complicated by iatrogenic Cushing syndrome and osteonecrosis of the knee. Identifying patients with autoimmune premature ovarian failure presents the opportunity to restore ovarian function by treating these patients with the proper immune modulation therapy. On the other hand, potent immune modulation therapy can have major complications. Corticosteroid therapy for autoimmune premature ovarian failure should be limited to use in placebo-controlled trials designed to evaluate the safety and efficacy of such treatment.

Adult↗

PubMed2004

Oral administration of desloratadine prior to sensitization prevents allergen-induced airway inflammation and hyper-reactivity in mice.

BACKGROUND: Histamine-1-receptor (H1R)-antagonists were shown to influence various immunological functions on different cell types and may thus be employed for immune-modulating strategies for the prevention of primary immune responses. OBJECTIVE: The aim of this study was to investigate the effects of an H1R-antagonist on allergen-induced sensitization, airway inflammation (AI) and airway hyper-reactivity (AHR) in a murine model. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) (six times, days 1-14) and challenged with aerosolized allergen (days 28-30). One day prior to the first and 2 h prior to every following sensitization, mice received either 1 or 0.01 microg of desloratadine (DL) or placebo per os. RESULTS: Sensitization with OVA significantly increased specific and total IgE and IgG1 serum levels, as well as in vitro IL-5 and IL-4 production by spleen and peribronchial lymph node (PBLN) cells. Sensitized and challenged mice showed a marked eosinophilic infiltration in broncho-alveolar lavage fluids and lung tissues, and developed in vivo AHR to inhaled methacholine. Oral treatment with DL prior to OVA sensitization significantly decreased production of OVA-specific IgG1, as well as in vitro Th2-cytokine production by spleen and PBLN cells, compared with OVA-sensitized mice. Moreover, eosinophilic inflammation and development of in vivo AHR were significantly reduced in DL-treated mice, compared with sensitized controls. CONCLUSION: Treatment with H1R-anatagonist prior to and during sensitization suppressed allergen-induced Th2 responses, as well as development of eosinophilic AI and AHR. This underscores an important immune modulating function of histamine, and implies a potential role of H1R-anatagonists in preventive strategies against allergic diseases.

Administration, Oral↗

PubMed1996

Immunologic alterations in bleomycin-treated mice: role of pulmonary fibrosis in the modulation of immune responses.

Among the side effects of bleomycin (BLM), a drug frequently used in the treatment of lymphomas and squamous-cell carcinomas, is pneumonitis with pulmonary fibrosis. The most prominent biochemical lesion associated with pulmonary fibrosis, a chronic debilitating and sometimes fatal disease, is an increase in the levels of collagen in the lung parenchyma. The mechanisms involved in the induction of this disease are still unclear, although results have suggested that the development of fibrosis may be immunologically mediated. There have, however, been no reports in the literature on the frequency and function of lymphocytes in the regional and systemic lymphoid tissues in BLM-induced pulmonary fibrosis. We therefore conducted a study, in which we inoculated C57Bl/6 mice intratracheally with BLM or saline, and tested the animals' lymphoid cells for various cell-mediated and humoral immune responses. The results indicated an increase in the number of lymphocytes in the lung-associated hilar lymph nodes, whereas the number of splenic lymphocytes was reduced as compared with control mice. Moreover, there was a significant inhibition of the antibody response to sheep erythrocytes in both the spleen and hilar lymph nodes of BLM-treated mice. Inhibition of the immune system appeared to be associated with the development of pulmonary fibrosis, and not to result from BLM toxicity, since the immune response of mice was not inhibited when they were injected with an identical dose of BLM under conditions that did not cause pulmonary fibrosis. Moreover, inhibition of splenic antibody responses was also observed in a hapten-induced model of pulmonary fibrosis, providing additional evidence that the induction of fibrosis and not the chemical toxicity of BLM was responsible for the modulation of immune responses.

Animals↗

PubMed1990

Modulation of immune responses with monoclonal antibodies. I. Effects on regional lymph node morphology and on anti-hapten responses to haptenized monoclonal antibodies.

Repeated injections of monoclonal antibody (mAb) culture supernatants into rat footpads increased the weights of the draining lymph nodes. Immunostained freeze sections showed that injection of MRC OX2, a mAb reacting with rat follicular dendritic cells and MRC OX7 (anti-Thy-1.1), led to gross hypertrophy primarily of the follicular areas, whereas MRC OX6 (anti-rat major histocompatibility complex class II molecules) resulted in selective stimulation of the paracortex. These findings indicate that mAb, when conjugated to certain antigens, would modulate the immune response to these antigens. Consequently, the mAb were conjugated with fluorescein isothiocyanate (FITC) and the humoral response against the hapten measured. The primary anti-FITC antibody response was tenfold stronger than after stimulation with FITC conjugated to a conventional carrier such as ovalbumin, and had some characteristics of a secondary response: a fast increase of IgG level to very high titers and a long duration without further amplification at later antigen challenges.

Adjuvants, Immunologic↗

PubMed2005

Human gene expression as a tool to determine horticultural maturity in a bioactive plant (Echinacea purpurea L. Moench).

A phenological study was conducted to determine the impact of harvest maturity on the immune-modulating properties of Echinacea purpurea. The aerial parts of this plant were collected during seven stages of development and were assayed for a common botanical marker for this species, cichoric acid. Plants of selected development stages were also assayed for total polysaccharides and compared for their immune-modulating effects on the THP-1 monocyte/macrophage cell line by means of a gene expression study. Although the concentration of cichoric acid did not change significantly during the course of the study, stage 1 (advanced vegetative) had the highest concentration of total polysaccharides and exhibited the most potent induction activity on immune-modulating cytokines such as interferon-gamma and tumor necrosis factor-alpha. These findings suggest that the use of gene expression may be an effective tool not only to standardize botanical extracts but also to optimize harvest time.

Biomarkers↗

PubMed1997

Various functions of PBMC from colon cancer patients are not decreased compared to healthy blood donors.

The immune surveillance hypothesis suggests impaired immune responses to participate in development of cancer. This may partly be due to increased amounts of PGE2 and histamine, which inhibit cellular immunity. These effects are mediated by cAMP, which is increased and thereby may down-regulate IL-2 and its receptor proteins in T helper cells. The proliferative responses and IL-2 synthesis of PBMC have earlier been shown to be reduced in patients with colon cancer. Recently immune modulating agents have been demonstrated to increase the proliferative response of PBMC in vitro, probably by inhibition of adenylate cyclase activity and induction of IL-2 mRNA expression. We have therefore studied the proliferative responses of PBMC from colon cancer patients to PWM and tested the effect of immune modulating agents, such as Serotonin, Sumatriptan, and Buspirone on these PBMC. We found no difference in levels of intracellular cAMP, IL-2 mRNA expression, IL-2R mRNA expression, or proliferative responses of PBMC from colon cancer patients compared to healthy blood donors. There was no effect of the immune modulating agents on PBMC from colon cancer patients.

Adult↗

PubMed2006

Combined prophylactic and therapeutic cancer vaccine: enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA-A2 mice.

We identified the strategies to induce a CTL response to human papillomavirus (HPV) 16 E2 in HLA-A2 transgenic mice (AAD). A chimeric HPV16 virus-like particle (VLP) that includes full length HPV16 E7 and E2 (VLP-E7E2) was generated. The combination of E2 and E7 has the advantage that E2 is expressed in early dysplasia and neoplasia lesions, where E7 is expressed in more advance lesions. Since T cell response to E2 is less defined, we first evaluated the strategies to enhancing CD8(+) T cell responses to HPV E7, using different combinations of immune-modulators with VLP-E7E2. Data showed that the CTL response to E7 could be significantly enhanced by coinjection of GM-CSF and anti-CD40 antibodies with chimeric VLP-E7E2 without adjuvant. However, using the same combination, a low level of CD8(+) T cell response to E2 was detected. To enhance the CD8+ T cell response to E2, we analyzed T cell epitopes from E2 sequence. A heterogenous prime-boost with chimeric VLP-E7E2 and E2 peptides was performed. The data showed that the priming with chimeric VLP-E7E2, followed by boosting with E2 peptides, gave a better CTL response than 2 immunizations with E2 peptides. The enhanced immunity is due to the increase of CD11c(+) and CD11c(+) CD40(+) double positive dendritic cells in mice that received immune-modulators, GM-CSF and anti-CD40. Furthermore, the level of anti-L1 antibodies remains similar in mice immunized with chimeric VLP with/without immune-modulators. Thus, the data suggested that the chimeric VLP-E7E2 has a therapeutic potential for the treatment of HPV-associated CINs and cancer without diminishing VLPs potential as a prophylactic vaccine by inducing anti-L1 antibodies against free virus.

Animals↗

PubMed2002

Interleukin 17 modulates the immune response to vaccinia virus infection.

Interleukin 17 (IL-17) is a newly identified cytokine that has a homolog in herpesvirus saimiri. We inserted murine IL-17 into vaccinia virus to study the role of IL-17 in viral infection. Vaccinia virus expressing IL-17 (vv-IL17) and its parental control virus (vv-pRB) grew to similar titers in vitro; however, vv-IL17 was more virulent in mice with a threefold lower LD(50) than for vv-pRB, and mean time to death of 2.8 days versus 4.5 days. Mice infected with vv-IL17 had higher titers of virus in the ovaries (P < 0.02) and showed a decrease in NK cell cytotoxicity (P < 0.02) on day 3 after infection. No significant difference was found in CTL activity. In addition, a significant decrease in IgG2a (P < 0.01) and increases in IgG1, IgG3, and IgA (P < 0.03) vaccinia virus-specific antibody titers were observed in mice infected with vv-IL17 versus vv-pRB, suggesting a Th-2-like response to infection. These data indicate that IL-17 modulates the immune response during virus infection.

Animals↗

PubMed2000

The Th1/Th2 paradigm in the pathogenesis of scleroderma, and its modulation by thalidomide.

The immunity generated in response to an antigenic stimulus can result in at least two distinct subclasses of immune responses, commonly referred to as Th1 and Th2. This review describes Th1- and Th2-type immune responses in animal models and in human mediated disease. Evidence obtained from working within these models suggests that manipulating the Th1/Th2 balance in the immune response can alter disease processes. The possible application of this strategy in scleroderma is presented. The immune modulating effects of the drug thalidomide on Th1 and Th2 immunity are also described, along with the drug's potential application to disease processes like scleroderma.

Animals↗

PubMed2001

Elements of angiotensin system are involved in leeches and mollusks immune response modulation.

We present immunocytochemical, biochemical and cellular evidences for the presence of a renin-angiotensin system (RAS) in coelomocytes of invertebrates (leech, Theromyzon tessulatum and mollusk Mytilus edulis). Leech coelomocytes are immunoreactive to polyclonal antisera raised against the T. tessulatum angiotensin-converting enzyme (ACE) and leech brain angiotensin II (AII) and a commercial anti-AT1 receptor. Biochemically, renin, ACE- and AT1-like receptor were identified in the leech immune cells. We further demonstrate that leech AII (10(-6) M) alone does not initiate nitric oxide (NO) release in invertebrate immunocytes but does only after pre-exposing the cells to IL-1 (15.9+/-2.6 nM; P<0.005 vs. 1.1 nM when AII is added alone). Similar results were obtained with human leukocytes (14.5+/-2.7 nM; P<0.005 IL-1+AII vs. 0.9 nM when AII is added alone). Then, an immunocytochemical study performed at the structural and ultrastructural levels confirmed the presence in same immune cells all the molecules of the renin-angiotensin system (RAS) in leeches as epitopes to IL-1-like protein and IL-1-like receptor. This is the first report in invertebrates and of a co-action between cytokines like substances and neuropeptides in an immune process and the involvement of the RAS in modulation of the immune response.

Angiotensins↗

PubMed2005

Consumption of purple sweet potato leaves modulates human immune response: T-lymphocyte functions, lytic activity of natural killer cell and antibody production.

AIM: To study the immunological effects of physiological doses of purple sweet potato leaves (PSPL). METHODS: The randomized crossover study (two periods, each lasting for 2 wk) involved 16 healthy non-smoking adults of normal weight. The 6-wk study consisted of a run-in (wk 1) PSPL diet (daily consumption of 200 g PSPL) or a control diet (low polyphenols, with the amount of carotenoids adjusted to the same level as that of PSPL) (wk 2-3), washout diet (wk 4), and switched diet (wk 5-6). Fasting blood was collected weekly in the morning. T-lymphocyte function was assessed via the proliferation and secretion of immunoreactive cytokines. Salivary IgA secretion and the specific cytotoxic activities of cytotoxic T lymphocytes and natural killer (NK) cells were determined. RESULTS: The plasma beta-carotene level increased with time in both groups, while the plasma polyphenol level decreased in the control group, and no significant difference was detected between the two groups. Although plasma polyphenol levels did not significantly increase in the PSPL group at the end of the study, they were significantly elevated in urine. PSPL consumption produced a significant increase in proliferation responsiveness of peripheral blood mononuclear cells (PBMC) and their secretion of immunoreactive IL-2 and IL-4. As well, lytic activity in NK cells was elevated in a time-dependent fashion. Salivary IgA secretion significantly decreased in control group after 2 wk, and returned to baseline following dietary switch to PSPL. CONCLUSION: Consumption of PSPL modulates various immune functions including increased proliferation responsiveness of PBMC, secretion of cytokines IL-2 and IL-4, and the lytic activity of NK cells. The responsible determinants of PSPL remain to be elucidated, as does the biological significance of the present observations.

Adult↗

PubMed1999

Soluble, high-affinity dimers of T-cell receptors and class II major histocompatibility complexes: biochemical probes for analysis and modulation of immune responses.

T cell receptors (TCR) and major histocompatibility complex (MHC) molecules are integral membrane proteins that have central roles in cell-mediated immune recognition. Therefore, soluble analogs of these molecules would be useful for analyzing and possibly modulating antigen-specific immune responses. However, due to the intrinsic low-affinity and inherent solubility problems, it has been difficult to produce soluble high-affinity analogs of TCR and class II MHC molecules. This report describes a general approach which solves this intrinsic low-affinity by constructing soluble divalent analogs using IgG as a molecular scaffold. The divalent nature of the complexes increases the avidity of the chimeric molecules for cognate ligands. The generality of this approach was studied by making soluble divalent analogs of two different classes of proteins, a TCR (2C TCR2Ig) and a class II MHC (MCCI-Ek2Ig) molecule. Direct flow cytometry assays demonstrate that the divalent 2C TCR2Ig chimera retained the specificity of the native 2C TCR, while displaying increased avidity for cognate peptide/MHC ligands, resulting in a high-affinity probe capable of detecting interactions that heretofore have only been detected using surface plasmon resonance. TCR2IgG was also used in immunofluorescence studies to show ER localization of intracellular peptide-MHC complexes after peptide feeding. MCCI-Ek2Ig chimeras were able to both stain and activate an MCC-specific T cell hybridoma. Construction and expression of these two diverse heterodimers demonstrate the generality of this approach. Furthermore, the increased avidity of these soluble divalent proteins makes these chimeric molecules potentially useful in clinical settings for probing and modulating in vivo cellular responses.

Base Sequence↗

PubMed1999

Onchocerciasis modulates the immune response to mycobacterial antigens.

Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce a type-1 immune response which is considered protective. Type-2 responses and diminished type-1 responses to mycobacteria have been previously correlated with active infection states such as pulmonary tuberculosis and lepromatous leprosy. The present study examines the immune responses of children exposed to both the helminth parasite Onchocerca volvulus and the mycobacterial infections, Mycobacterium tuberculosis and M. leprae. Proliferation of peripheral blood mononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing microfilarial (MF) density. Although interferon-gamma (IFN-gamma) production strongly correlated with cellular proliferation, it was surprisingly not related to MF density for either antigen. IL-4 production in response to helminth antigen and PPD increased with ascending children's age. IFN-gamma and cellular proliferation to PPD were not related to age, but in response to helminth antigen were significantly higher in children of age 9-12 years than children of either the younger age group (5-8 years) or the older group (13-16 years). Thus, there was a MF density-related down-regulation of cellular responsiveness and age-related skewing toward type 2 which was paralleled in response to both the helminth antigen and PPD. This parasite-induced immunomodulation of the response to mycobacteria correlates with a previous report of doubled incidence of lepromatous leprosy in onchocerciasis hyperendemic regions. Moreover, this demonstration that helminth infection in humans can modulate the immune response to a concurrent infection or immunological challenge is of critical importance to future vaccination strategies.

Adolescent↗

PubMed1995

Role of IL-4 and IFN-gamma in modulation of immunity to Borrelia burgdorferi in mice.

Because T cells appear to modulate the severity of murine Borrelia burgdorferi infections, we decided to examine the possible involvement of T cell-associated cytokines in disease outcome. Comparison of in vitro B. burgdorferi Ag-induced cytokine production in disease-susceptible and -resistant strains revealed striking differences; spleen cells from susceptible C3H mice produced significantly higher levels of IL-2 and IFN-gamma and lower levels of IL-4 than spleen cells from resistant BALB/c mice. Lymph node responses were even more divergent, with C3H mice producing high levels of IFN-gamma, and BALB/c mice producing little or none. This apparent Th1/Th2 cytokine imbalance was also reflected in vivo, since serum from C3H had significantly higher levels of B. burgdorferi-specific IgG2a Ab and lower levels of IgG1 Ab than serum from BALB/c mice. In vivo studies confirmed the importance of IL-4 in early control of spirochete growth, since treatment of either strain with neutralizing anti-IL-4 mAb led to increased joint swelling and higher spirochete burdens in joints compared with those in control mAb-treated mice. In contrast, IFN-gamma may hinder early control of spirochete growth in susceptible C3H mice, since treatment of mice with neutralizing anti-IFN-gamma mAb reduced both joint swelling and joint spirochete burdens compared with those in control mAb-treated mice. These studies indicate opposing roles for IL-4 and IFN-gamma in the modulation of spirochete growth and disease development in B. burgdorferi-infected mice and suggest that differential cytokine production early in infection may contribute to strain-related differences in susceptibility.

Animals↗

PubMed2005

Eicosapentaenoic acid modulates the immune response but has no effect on a mimic of antigen-specific responses.

OBJECTIVE: It has been suggested that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) has immunosuppressive effects and that these may be detrimental in some circumstances. Many studies have used high-fat diets or have concentrated on one aspect of immune function, such as mitogen-induced proliferation. In the present study we assessed the effect of high-purity EPA provided as a novel diester with propane-1,3-diol, which was delivered orally within the normal dietary fat content. METHODS: Mitogen-induced proliferation and a mimic of antigen-specific splenocyte proliferation were examined. Proinflammatory cytokine production in response to lipopolysaccharide ex vivo was also measured. Balb/c mice were fed a fat-free diet to which was added oil to make up 5% of the final diet weight by using corn oil or 95% pure EPA as a diester with propane-1,3-diol (4%, plus 1% corn oil). RESULTS: There was no difference in food consumption or weight gain between mice fed the control and EPA-enriched diets for 10 or 24 d. There was a significant decrease in the splenocyte proliferation index in animals fed the EPA-enriched diet after 10 and 24 d when stimulated by concanavalin A (P<0.05), but no difference when cells were stimulated with anti-CD3 and interleukin-2. There was a significant increase in the production of tumor necrosis factor by splenocytes of mice fed the EPA-enriched diet when stimulated by lipopolysaccharide (P<0.0005). However, there was no difference in ex vivo lipopolysaccharide-stimulated production of interleukin-6 between the two diets at either time point (P>0.05). CONCLUSIONS: The present study found that, rather than producing a generalized immunosuppression, the administration of approximately 10 g of EPA/kg of body weight has more subtle effects in modulating the immune system. The observed effects of EPA may explain some of its reported beneficial effects in inflammatory conditions without producing detrimental effects on antigen-specific immunosurveillance.

Animals↗

PubMed2002

Global gene profiling in human endometrium during the window of implantation.

Implantation in humans is a complex process that is temporally and spatially restricted. Over the past decade, using a one-by-one approach, several genes and gene products that may participate in this process have been identified in secretory phase endometrium. Herein, we have investigated global gene expression during the window of implantation (peak E2 and progesterone levels) in well characterized human endometrial biopsies timed to the LH surge, compared with the late proliferative phase (peak E2 level) of the menstrual cycle. Tissues were processed for poly(A(+)) RNA and hybridization of chemically fragmented, biotinylated cRNAs on high density oligonucleotide microarrays, screening for 12,686 genes and expressed sequence tags. After data normalization, mean values were obtained for gene readouts and fold ratios were derived comparing genes up- and down-regulated in the window of implantation vs. the late proliferative phase. Nonparametric testing revealed 156 significantly (P < 0.05) up-regulated genes and 377 significantly down-regulated genes in the implantation window. Up-regulated genes included those for cholesterol trafficking and transport [apolipoprotein (Apo)E being the most induced gene, 100-fold], prostaglandin (PG) biosynthesis (PLA2) and action (PGE2 receptor), proteoglycan synthesis (glucuronyltransferase), secretory proteins [glycodelin, mammaglobin, Dickkopf-1 (Dkk-1, a Wnt inhibitor)], IGF binding protein (IGFBP), and TGF-beta superfamilies, signal transduction, extracellular matrix components (osteopontin, laminin), neurotransmitter synthesis (monoamine oxidase) and receptors (gamma aminobutyric acid A receptor pi subunit), numerous immune modulators, detoxification genes (metallothioneins), and genes involved in water and ion transport [e.g. Clostridia Perfringens Enterotoxin (CPE) 1 receptor (CPE1-R) and K(+) ion channel], among others. Down-regulated genes included intestinal trefoil factor (ITF) [the most repressed gene (50-fold)], matrilysin, members of the G protein-coupled receptor signaling pathway, frizzled-related protein (FrpHE, a Wnt antagonist), transcription factors, TGF-beta signaling pathway members, immune modulators (major histocompatibility complex class II subunits), and other cellular functions. Validation of select genes was conducted by Northern analysis and RT-PCR using RNA from endometrial biopsies obtained in the proliferative phase and the implantation window and by RT-PCR using RNA from cultured endometrial epithelial and stromal cells. These approaches confirmed up-regulation of genes corresponding to IGFBP-1, glycodelin, CPE1-R, Dkk-1, mammaglobin, and ApoD and down-regulation for PR membrane component 1, FrpHE, matrilysin, and ITF, as with the microarray data. Cultured endometrial epithelial cells were found to express mRNAs for glycodelin, CPE-1R, Dkk-1, the gamma aminobutyric acid A receptor pi subunit, mammaglobin, matrilysin, ITF and PR membrane component 1. The expression of IGFBP-1, CPE1-R, Dkk-1, and ApoD mRNAs increased upon decidualization of stromal cells in vitro with progesterone after E2 priming, whereas FrpHE decreased, consistent with the microarray results. Overall, the data demonstrate numerous genes and gene families not heretofore recognized in human endometrium or associated with the implantation process. Reassuringly, several gene products, known to be differentially expressed in the implantation window or in secretory endometrium, were verified, and the striking regulation of select secretory proteins, water and ion channels, signaling molecules, and immune modulators underscores the important roles of these systems in endometrial development and endometrial-embryonic interactions. In addition, the current study validates using high density oligonucleotide microarray technology to investigate global changes in gene expression in human endometrium.

Adult↗

PubMed1991

Corticotropin-releasing factor modulates the immune response to stress in the rat.

We examined the role of CRF, a key mediator of the endocrine response to stress, in modulating immunosuppression during the subacute stress of intermittent electrical shock over 1 h. Administration of shock to intact rats resulted in a 74% decrement in T-lymphocyte proliferation and a 59% decrease in natural killer cytotoxicity. Similar suppression of these two parameters of immune function in response to shock was noted in adrenalectomized rats as well. The immunosuppressive effects of this shock were significantly and comparably blunted when both intact and adrenalectomized animals were pretreated 1) iv with either a highly potent polyclonal CRF antibody or a specific CRF antagonist or 2) intracerebroventricularly with either a high affinity monoclonal antibody to CRF or a specific CRF antagonist. An immunomodulatory role for CRF is further supported by the findings that administration of exogenous CRF, either iv (10 micrograms/animal) or intracerebroventricularly (1 microgram/animal), resulted in significant decrements in lymphocyte proliferation and natural killer cytotoxicity, similar to those seen with the stress paradigm. Our observations indicate that CRF plays a significant role in modulating the immune response to subacute stress, largely by adrenal-independent mechanisms.

Adrenalectomy↗