Biomedical subjects

F Takei

Publications and source records attributed to F Takei.

At least 37 records · Page 2Linked to original sources

PubMed1998

Dominant-negative effect of the lymphocyte function-associated antigen-1 beta (CD18) cytoplasmic domain on leukocyte adhesion to ICAM-1 and fibronectin.

The cytoplasmic domains of LFA-1 (CD11a/CD18) are thought to play an important role in the regulation of LFA-1 function. To further elucidate the role of the LFA-1 cytoplasmic domains, we transfected chimeric proteins consisting of the extracellular domain of CD4 fused with the transmembrane and cytoplasmic domains of LFA-1 into T and B cell lines, EL-4 and A20, respectively, and examined their effects on LFA-1-mediated cell adhesion. The CD4/18, but not CD4/11a, chimera profoundly inhibited LFA-1-mediated cell adhesion to ICAM-1, as well as cell spreading following cell adhesion. Unexpectedly, cell adhesion to fibronectin was also inhibited by the CD4/18 chimera. The CD4/18 chimera did not affect the expression of endogenous LFA-1 or the association of CD11a and CD18. Truncation of the carboxyl-terminal 13 amino acid residues of the CD18 cytoplasmic domain of the chimera completely abrogated the inhibitory effect on LFA-1. Among these amino acid residues, the carboxyl-terminal six residues were dispensable for the inhibitory effect in EL-4 cells, whereas it significantly reduced the inhibitory activity of CD4/18 in A20 cells. A larger truncation of the CD18 cytoplasmic domain was needed to fully abrogate the inhibitory effects of CD4/18 on the adhesion to fibronectin. These results show that 1) the CD4/18 chimera has dominant-negative effects on cell adhesion mediated by LFA-1 as well as fibronectin receptors, and 2) amino acid residues of the CD18 cytoplasmic domain involved in the inhibition of LFA-1 seem to be different from those for fibronectin receptors.

Amino Acid Sequence↗

PubMed1998

Localization of five new Ly49 genes, including three closely related to Ly49c.

Nine genes belonging to the mouse Ly49 multigene family of natural killer cell receptors have been identified to date. Two of these genes, Ly49h and i, are very closely related to the well characterized Ly49c gene in the carbohydrate recognition domain. Here we show by Southern blotting that at least two additional new sequences exist in C57BL/6 mice that are also closely related to Ly49c in the carbohydrate recognition domain. Furthermore, in contrast to Ly49a, extensive variation in the arrangement and number of Ly49c-related genes in different mouse strains was observed. To characterize and localize the new Ly49c-related genes in C57BL/6 mice, we isolated and mapped genomic P1 clones hybridizing to an Ly49C exon 7 probe. Locations and the relative order of all Ly49 genes found within the clones was determined. We also used polymerase chain reaction to sequence exons 2, 4, and 7 from all genes. In this manner, we identified five new potential Ly49 genes which have been tentatively termed Ly49j-n. Ly49j, k, and n belong to the Ly49c-related subfamily, whereas Ly49l and Ly49m are most similar to Ly49d and g, respectively. Interestingly, the members of the Ly49c-related subfamily are not clustered as a unit but are interspersed among other Ly49 genes. These results illustrate the complex nature of the Ly49 gene family and should aid in the understanding of functions, such as the mediation of hybrid resistance, in which Ly49c-related genes play a role.

Animals↗

PubMed1998

Induction of sensitivity to NK-mediated cytotoxicity by TNF-alpha treatment: possible role of ICAM-3 and CD44.

SR-91 is a natural killer (NK)-resistant leukemic cell line expressing a low level of ICAM-1. Pre-treatment of SR-91 cells with TNF-alpha or IFN-gamma, increased both ICAM-1 (CD54) expression on SR-91 cells and binding to the human NK cell line NK-92. However, only TNF-alpha-treated SR-91 cells became sensitive to killing by NK-92 cells. The increased binding induced by both cytokines and the TNF-alpha-induced sensitivity of SR-91 cells to NK-92 cell killing were abrogated by anti-LFA-1 mAb as well as by a combination of antibodies against the three ligands of LFA-1 (CD11a/CD18), ICAM-1 (CD54), ICAM-2 (CD102) and ICAM-3 (CD50). This indicated that LFA-1 interaction with the three ICAMs on SR-91 cells is essential for effector-target cell binding (which is a prerequisite for subsequent target cell lysis), but is insufficient to render the SR-91 cells sensitive to killing by NK-92 cells. TNF-alpha, but not IFN-gamma also induced the activation of LFA-1, CD44 and beta1 integrins on SR-91 cells. Based on these observations we propose that the differential effect of TNF-alpha and IFN-gamma could be related to the activation of certain adhesion molecules on the surface of SR-91 cells by TNF-alpha that, upon interaction with their counter-receptors on NK-92 cells, lead to the activation of the NK-92 cells.

Antigens, CD↗

PubMed1998

Regulation of intracranial pressure in the rat with chronic moderate hypercapnia.

STUDY OBJECTIVES: In this animal study we investigated whether CO2-induced intracranial hypertension was sustained in chronic hypercapnia. DESIGN: We kept five rats in a 10% CO2-air mixture (PaCO2 73.4 +/- 6.2 Torr, mean +/- 1SD) for 22 weeks, and then measured the rats' intracranial pressure while breathing the 10% CO2- air mixture or the room air. RESULTS: The intracranial pressures recorded during chronic hypercapnia in systole and diastole were 7.0 +/- 1.9 and 5.4 +/- 1.6 mm Hg, respectively. When the rats were acutely exposed to the room air (PaCO2, 51.9 +/- 10.2 Torr), the intracranial pressures in systole and diastole were 6.1 +/- 1.4 and 5.0 +/- 0.8 mm Hg, respectively, were not significantly different from those during hypercapnia (P>0.05, paired t-test). CONCLUSIONS: The intracranial pressure in rats with chronic moderate hypercapnia was not significantly different from normocapnic rats, and this change was associated with a blunting of intracranial pressure autoregulation.

Animals↗

PubMed1997

The role of LFA-1 (CD11a/CD18) cytoplasmic domains in binding to intercellular adhesion molecule-1 (CD54) and in postreceptor cell spreading.

We have investigated the role of the cytoplasmic domains of LFA-1 in binding to ICAM-1 and in postadhesion events. Various truncated and chimeric forms of LFA-1 alpha (CD11a) and beta (CD18) chains were generated and transfected into murine fibroblast TNR-2 cells. Transfected fibroblasts expressing wild-type LFA-1 adhered only weakly to ICAM-1 immobilized on plastic, and phorbol ester pretreatment enhanced this adhesion significantly. In contrast, transfected cells expressing LFA-1 lacking both the alpha and the beta cytoplasmic domains, the beta cytoplasmic domain alone, or GPI-anchored LFA-1 adhered to immobilized ICAM-1 without prior activation. Truncation of the alpha cytoplasmic domain alone resulted in much reduced cell adhesion which could be only weakly upregulated by PMA. The presence of manganese dramatically enhanced the binding to ICAM-1 of LFA-1 lacking the alpha cytoplasmic domain or both cytoplasmic domains, whereas it had relatively little effect on wild-type LFA-1 or the mutant lacking the beta cytoplasmic domain. Soluble LFA-1, generated by phosphatidylinositol-specific phospholipase-C treatment of GPI-anchored LFA-1, was capable of binding ICAM-1+ cells. Although doubly truncated or GPI-anchored LFA-1 mediated cell adhesion to immobilized ICAM-1, cells expressing these mutants, as well as those expressing individual alpha and beta chain truncations, failed to spread out following this adhesion, whereas the wild-type transfectants did so readily. Manganese had no effect on cell spreading. Fluorescent staining of these cells indicated no significant variation in the distribution of LFA-1 on the cell surface. From these results we conclude that (1) cells expressing LFA-1 lacking both the alpha and the beta cytoplasmic domains adhere to ICAM-1 without prior stimulation, indicating the importance of LFA-1 cytoplasmic domains in inside-out signaling, (2) truncation of the alpha cytoplasmic domain alone inhibits cell adhesion by making LFA-1 nonresponsive to inside-out signaling, and (3) both cytoplasmic domains are required for cell spreading following adhesion to immobilized ICAM-1.

3T3 Cells↗

PubMed1997

ICAM-2 provides a costimulatory signal for T cell stimulation by allogeneic class II MHC.

To examine the functional role of intercellular adhesion molecule (ICAM)-2 (CD102) in antigen presentation to T cells, the I-E(d)-transfected murine fibroblastic L cell line RT10.3 (H-2(k)) was transfected with murine ICAM-1 or ICAM-2 and tested for their abilities to stimulate C3H/He (H-2(k)) splenic T cells. The expression of ICAM-1 or ICAM-2 on RT10.3 cells significantly increased the stimulation of T cells in an LFA-1 (CD11a/CD18)-dependent manner as determined by thymidine incorporation. This enhanced T cell response was also observed when combinations of untransfected RT10.3 cells and ICAM-1- or ICAM-2-transfected L cells were used as stimulators, indicating that ICAM-1 and ICAM-2 deliver a costimulatory signal instead of merely enhanced T cell adhesion to antigen presenting cells. The T cells stimulated with ICAM-transfected RT10.3 in the primary response vigorously responded to BALB/c (H-2(d)) spleen cells in a secondary allogeneic stimulation. In contrast, T cells stimulated with untransfected RT10.3 in the primary response did not respond to BALB/c spleen cells in the secondary response. Significant secondary responses to a third party stimulator, C57BL/6 spleen cells (H-2(b)), were observed regardless of ICAM expression on RT10.3 cells in the primary stimulation. These results indicate that ICAM-2 as well as ICAM-1 not only enhance antigen presentation mediated by allogeneic class II MHC but also provide a costimulatory signal to T cells. This costimulatory signal may be important in the aversion of an anergic state.

Animals↗

PubMed1997

The NK2.1 receptor is encoded by Ly-49C and its expression is regulated by MHC class I alleles.

A dual receptor system composed of activation and inhibitory receptors apparently controls NK cell-mediated lysis. In the C57BL/6 mouse, the NK1.1 molecule acts as an activation receptor whereas Ly-49A, C and G2 can inhibit NK cell lysis of target cells expressing specific MHC class I molecules. We previously reported that NK2.1 is an activation receptor sharing structural properties with members of the NKR-P1 and Ly-49 receptor families. In this study, we have shown that NK2.1 is encoded by the previously described Ly-49C gene. We also found that the expression level of NK2.1/Ly-49C is modulated by H-2-dependent factors and that this regulation differs from that previously described for Ly-49A. Flow cytometry analyses of NK-enriched spleen cells from MHC congenic strains on C57BL/10 and BALB/c backgrounds indeed revealed that the level of NK2.1/Ly-49C expression, but not the number of positive cells, is low in strains expressing H-2b and H-2k haplotypes as compared to H-2d mice. Similar analyses of splenic NK cells from two series of congenic and congenic recombinant strains on the C57BL/10 background indicate that the main regulatory element(s) are most likely the H-2Kb and H-2Dk alleles. Together with our and others previous observations, these results identify the NK2.1/Ly-49C antigen as a receptor for MHC class I molecules whose expression is regulated by host MHC genes.

Alleles↗

PubMed1997

The Ly-49 family: genes, proteins and recognition of class I MHC.

The Ly-49 family consists of at least nine members, of which Ly-49A and C have been found to be NK-cell inhibitory receptors specific for class I MHC. The functions of other Ly-49 molecules are still unclear. Further analysis of Ly-49 is complicated by the cross-reactivities of some anti-Ly-49 antibodies initially thought to be specific for individual Ly-49 molecules. Studies on the role of Ly-49 in hybrid resistance as well as on allelic exclusion are also complicated by our recent finding that a novel Ly-49CB6 gene is the likely allelic form of Ly-49CBALB as opposed to a previously reported highly related but distinct gene in B6 mice. In cell-cell binding assays, only Ly-49A and C show significant binding to class I MHC. Ly-49A and C also bind some polysaccharides, and carbohydrates on class I MHC seem to be important for its binding to Ly-49. However, this interaction involves not only the carbohydrate recognition domain of Ly-49 but also a part of the stalk region, suggesting that both carbohydrates and peptide backbone of class I MHC may be recognized by Ly-49. It is likely that additional Ly-49 molecules yet to be identified function as NK-inhibitory receptors specific for class I MHC.

Animals↗

PubMed1996

Heterogeneity among Ly-49C natural killer (NK) cells: characterization of highly related receptors with differing functions and expression patterns.

Ly-49C is a member of the polymorphic family of murine NK cell inhibitory receptors. The 5E6 antibody that defines a subset of NK cells responsible for the rejection of parental H-2d bone marrow by F1 mice has been shown previously to react with Ly-49C. Here, the 5E6 antibody was found to detect two Ly-49C-related molecules in B6 mice. Two cDNA clones were isolated from B6 NK cells, one identical to previously reported Ly-49CB6 and the other a novel cDNA. The deduced amino acid sequence of the latter differs from that of Ly-49CBALB at only 4 residues, whereas the previously reported Ly-49CB6 differs at 22 residues. Flow cytometric analyses of COS cells transfected with the two cDNAs showed that the 5E6 antibody binds to both Ly-49 molecules, while another anti-Ly-49C antibody, 4LO3311, binds to the newly described Ly-49C but not the previously reported Ly-49CB6. Two-color flow cytometric analysis detected 5E6+4LO3311- as well as 5E6+4LO3311+ subsets of NK cells from B6, but not BALB/c, mice. The level of Ly-49C expression on B6 NK cells detected by the 4LO3311 antibody was substantially lower than that on BALB/c NK cells. Binding specificity of the novel Ly-49CB6 was indistinguishable from that of Ly-49CBALB, whereas no binding was detectable with previously reported Ly-49CB6. These results demonstrate that the newly described Ly-49CB6, not the previously reported Ly-49CB6, is the probable B6 allelic form of Ly-49C. The previously reported Ly-49CB6 must be encoded by a separate gene and should be renamed Ly-49I. The implication of these results with respect to the role of Ly-49C in hybrid resistance is discussed.

Amino Acid Sequence↗

PubMed1996

The roles of CD11/CD18 and ICAM-1 in acute Pseudomonas aeruginosa-induced pneumonia in mice.

Neutrophil accumulation in response to Pseudomonas aeruginosa in the lungs is mediated through CD11/CD18. This study determined the roles of CD11a, CD11b, and intercellular adhesion molecule (ICAM)-1 in P. aeruginosa-induced pneumonia and compared the function of ICAM-1 using Abs or ICAM-1 mutant mice. Anesthetized BALB/c mice pretreated with either Abs against CD11a, CD11b, ICAM-1, or rat IgG received intratracheal instillation of P. aeruginosa for 4 h. In other studies, ICAM-1 mutant and wild-type mice received either anti-ICAM-1 Ab or rat IgG followed by instillation of P. aeruginosa. The data show that Abs against CD11a, CD11b, and ICAM-1 in BALB/c mice inhibited neutrophil emigration by 79, 81, and 56%, respectively. ICAM-1 mutant mice showed no inhibition of neutrophil emigration compared with wild-type mice. Pretreatment with anti-ICAM-1 Ab inhibited neutrophil emigration in wild-type (129/SvxC57) mice by 67% but had no effect in ICAM-1 mutant mice, suggesting that the Ab was acting specifically through recognition of its Ag. We conclude that CD11a and CD11b are required for neutrophil emigration. The observed function of ICAM-1 varies depending on the method by which it is inhibited. Abs may overestimate function by altering other cellular functions or mutant mice may develop alternative pathways of emigration.

Acute Disease↗

PubMed1996

The role of P-selectin and ICAM-1 in acute lung injury as determined using blocking antibodies and mutant mice.

Cobra venom factor (CVF) induces lung injury through oxidant- and neutrophil-dependent mechanisms. Adhesion molecules, particularly L-selectin, P-selectin, CD11/CD18, and ICAM-1, are required for full expression of injury in rats. This study compared the roles of P-selectin and ICAM-1 using either mutant mice or blocking Abs. Mice deficient in either P-selectin, ICAM-1, or both adhesion molecules were compared with wild-type mice. Wild-type and single mutant mice were given Abs against murine P-selectin or ICAM-1. CVF was injected i.v., and neutrophil sequestration and extravascular albumin were measured 30 min later. Neither P-selectin, ICAM-1, nor P-selectin/ICAM-1 double mutants showed a reduction in neutrophil sequestration or lung injury when compared with wild-type mice. Anti-P-selectin Abs inhibited both sequestration and injury in wild-type mice by 57% and 60%, respectively, but had no effect in P-selectin mutants. Similar results were found using anti-ICAM-1 Ab in wild-type mice (78% inhibition of sequestration and 88% inhibition of injury) and ICAM-1 mutant mice (no reduction). These results suggest that the apparent role of these molecules in CVF-induced lung injury depends on the method used to block function. When studied using blocking Abs, both P-selectin and ICAM-1 were required for neutrophil sequestration and lung injury, while neither played a role singly or together when studied using mice with genetic deletions. Abs may inhibit neutrophil sequestration and lung injury through mechanisms other than simply adhesion blockade, or mutant mice may utilize alternative adhesion pathways.

Animals↗

PubMed1996

Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes.

The murine heat-stable antigen (HSA) is a glycosyl-phosphatidylinositol-linked cell surface protein which has been implicated in cellular adhesion processes, the co-stimulation of CD4+ T cells, and B cell memory. We have recently demonstrated a significant reduction in pro-B and pre-B lymphocytes in transgenic mice that overexpress HSA. We now report that cross-linking HSA with the M1/69 monoclonal antibody induces the apoptosis of cultured B cell precursors in a stomal cell and cytokine-independent manner and that sensitivity to HSA-mediated cell death increases with developmental maturity. The cross-linking of HSA does not induce apoptosis in mature splenic B cells, but instead inhibits their ability to proliferate in response to anti-CD40 + IL-4. Taken together, these data implicate HSA as a potent negative regulator of B cell development and activation.

Animals↗

PubMed1996

Characterization of murine intercellular adhesion molecule-2.

Rat mAbs were raised against murine intercellular adhesion molecule-2 (ICAM-2). Immune precipitation and purification reveal that the murine ICAM-2 glycoprotein is 55 kDa and is similar in size to human ICAM-2. ICAM-2 is expressed on a variety of leukocyte cell lines, including T and B lymphoma, mastocytoma, and macrophage lines. ICAM-2 is well expressed on endothelioma cell lines, and in contrast to ICAM-1, expression is not increased by inflammatory cytokines. One of the mAb to ICAM-2 partially or completely inhibits binding of cells expressing LFA-1 to purified ICAM-2, and binding of cells expressing ICAM-2 to purified LFA-1. The findings in the mouse are congruent with those in the human, suggesting functional conservation of ICAM-2 across species.

Animals↗

PubMed1996

Role of the intercellular adhesion molecule-1(ICAM-1) in endotoxin-induced pneumonia evaluated using ICAM-1 antisense oligonucleotides, anti-ICAM-1 monoclonal antibodies, and ICAM-1 mutant mice.

This study examined the effectiveness of antisense oligonucleotides targeted to intercellular adhesion molecule-1 (ICAM-1) to inhibit endotoxin-induced upregulation of ICAM-1 and neutrophil emigration and compared the apparent role of ICAM-1 when examined using antisense oligonucleotides, anti-ICAM-1 antibodies, and ICAM-1 mutant mice. Antisense oligonucleotides inhibited upregulation of ICAM-1 mRNA at 4 and 24 h after instillation of endotoxin in a dose-dependent manner. Neutrophil emigration into the alveolar spaces at 24 h was inhibited by 59%, similar to inhibition using the anti-ICAM-1 antibodies 3E2 (58%) and YN1/1 (75%). No inhibition was observed in the ICAM-1 mutant compared to wild-type mice. These data show that antisense oligonucleotides targeted to ICAM-1 inhibit the endotoxin-induced upregulation of ICAM-1 in the lung and are as effective as anti-ICAM-1 antibodies in preventing neutrophil emigration. The incomplete inhibition by either antisense oligonucleotides or antibodies suggests that alternative adhesion pathways that do not require ICAM-1 are important in neutrophil emigration in the lungs. The disparity in the role of ICAM-1 when evaluated using antisense or antibodies compared to mutant mice suggests that either these inhibitors are exerting additional effects on endothelial cells other than blockade of ICAM-1 or mutant mice have upregulated the ICAM-1-independent pathways to compensate for the long-term loss of ICAM-1.

Animals↗

PubMed1996

Recognition of class I major histocompatibility complex molecules by Ly-49: specificities and domain interactions.

Ly-49 is a family type II transmembrane proteins encoded by a gene cluster on murine chromosome 6. One member of this family, Ly-49A, is expressed by a natural killer (NK) cell subset, binds to class I major histocompatibility complex (MHC) molecules, and blocks the killing of target cells bearing the appropriate H-2 antigens. Here we show that another member of this family which is expressed by an NK cell subset, Ly-49C, recognizes H-2b and H-2d structures which are distinct from and overlapping with those recognized by Ly-49A. Interactions between Ly-49A and C and their class I ligands are entirely blocked by the antibodies 5E6, YE1/48, YE1/32, and A1, all of which were found to recognize epitopes contained within the carbohydrate recognition domain (CRD). However, cell-cell binding assays revealed that class I binding specificity is conferred by a combination of sequences within both the CRD and a 19-amino acid adjacent region. We also investigated the question of whether Ly-49A and C form dimers on cells which express both receptors. When coexpressed on COS cells, sequential immunoprecipitation demonstrated that these receptors pair exclusively as homodimers, with no evidence for heterodimeric structures. These observations provide insight into both the biochemical nature of the Ly-49 family as well as the receptor functions of Ly-49C on NK cells.

Amino Acid Sequence↗

PubMed1996

Reduction of early B lymphocyte precursors in transgenic mice overexpressing the murine heat-stable antigen.

To study the role of the murine heat-stable Ag (HSA) in lymphocyte maturation, we generated transgenic mice in which the HSA cDNA was under the transcriptional control of the TCR V beta promoter and Ig mu enhancer. The HSA transgene was expressed during all stages of B lymphocyte maturation. Expression was first detected in the earliest lymphoid-committed progenitors, which normally do not express HSA, and subsequently reached the highest levels in pro- and pre-B cells. In bone marrow, the number of IL-7-responsive clonogenic progenitors was < 4% of normal, whereas the frequency of earlier B lymphocyte-restricted precursors, detectable as Whitlock-Witte culture-initiating cells, was normal. Pro- and pre-B cells detected by flow cytometry were reduced by approximately 50% relative to controls. Mature splenic B cells were also reduced but to a lesser extent than in marrow, and their response to LPS stimulation was impaired. Reconstitution of SCID and BALB/c-nu/nu mice with HSA transgenic marrow indicated that the perturbations in B lymphopoiesis were not caused by a defective marrow microenvironment or by abnormal T cells. Our previous studies showed elevated HSA expression throughout thymocyte development, which resulted in a profound depletion of CD4+CD8+ double-positive and single-positive thymocytes. Together, these results indicate that HSA levels can determine the capacity of early T and B lymphoid progenitors to proliferate and survive. Therefore, HSA could serve as an important regulator during the early stages of B and T lymphopoiesis.

Animals↗

PubMed1996

Neurovascular developmental interaction: a specific form of vascular maldevelopment in the malformed brain. I. An experimental study and proposal of a new teratological concept.

The process of the development of the intracranial vessels was studied by means of immunohistochemical analysis of factor VIII in normal and exencephalic chick fetuses. The results revealed that the development of blood vessels in exencephalic brain was far advanced beyond the norm, with intense immunoreactivity to factor VIII on postincubation day 16 exceeding that on day 21 in normal controls. Compared with results regarding the direction of the overgrowth in the neuronal maturation process in the previous study using the chick exencephaly model, the findings of overmatured blood vessels were compatible with NSE- and somatostatin-positive elements that appeared especially in the overgrowth foci. The results of the present study suggested the pathogenic development of the "area cerebrovasculosa" in the neural placode as a phenomenon consequent upon hypervascularization in response to neuronal overgrowth, as seen in human cases of exencephaly or anencephaly. We emphasize the significance of this specific phenomenon in the development of the fetal central nervous system, namely neurovascular developmental interaction.

Animals↗

PubMed1996

New insights into the regulation of ICAM-1 gene expression.

Cell-cell adhesion is critical in the generation of effective immune responses and is dependent upon the expression of a variety of cell surface receptors. Intercellular adhesion molecule-1 (ICAM-1; CD54) is an inducible cell surface glycoprotein expressed at a low level on a subpopulation of hematopoietic cells, vascular endothelium, fibroblasts, and certain epithelial cells. However, its expression is dramatically increased at sites of inflammation, providing important means of regulating cell-cell interactions and thereby inflammatory responses. Inasmuch the modulation of ICAM-1 expression during inflammation by pharmacologic agents might be very attractive for medical treatment, the intracellular regulatory elements and signaling pathways underlying the inducible expression of ICAM-1 by proinflammatory cytokines remain largely unknown. In this review, a novel posttranscriptional regulation of ICAM-1 gene expression by two inflammatory mediators, interferon-gamma and phorbol myristate acetate, and the possible role of the serine/threonine phosphorylation pathway in the cycloheximide-induced ICAM-1 message stabilization are discussed in light of our current understanding of ICAM-1 gene regulation during an inflammatory response.

Animals↗