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Hidero Kitasato

Publications and source records attributed to Hidero Kitasato.

At least 19 recordsLinked to original sources
PubMed2007

Lipopolysaccharide-induced up-regulation of triggering receptor expressed on myeloid cells-1 expression on macrophages is regulated by endogenous prostaglandin E2.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface molecule that is expressed by neutrophils and monocytes. TREM-1 expression is modulated by various ligands for TLRs in vitro and in vivo. However, the influence of PGE(2), a potential mediator of inflammation, on TREM-1 expression has not been elucidated. In this study, we examined the effects of PGE(2) on LPS-induced TREM-1 expression by resident murine peritoneal macrophages (RPM) and human PBMC. PGE(2) significantly induced murine TREM-1 (mTREM-1) expression by RPM. Up-regulation of TREM-1 expression was specific to PGE(2) among arachidonic acid metabolites, while ligands for chemoattractant receptor-homologous molecule expressed on Th2 cells and the thomboxane-like prostanoid receptor failed to induce mTREM-1 expression. PGE(2) also increased expression of the soluble form of TREM-1 by PBMC. LPS-induced TREM-1 expression was regulated by endogenous PGE(2) especially in late phase (>2 h after stimulation), because cyclooxygenase-1 and -2 inhibitors abolished this effect at that points. A synthetic EP4 agonist and 8-Br-cAMP also enhanced mTREM-1 expression by RPM. Furthermore, protein kinase A, PI3K, and p38 MAPK inhibitors prevented PGE(2)-induced mTREM-1 expression by RPM. Activation of TREM-1 expressed on PGE(2)-pretreated PBMC by an agonistic TREM-1 mAb significantly enhanced the production of IL-8 and TNF-alpha. These findings indicate that LPS-induced TREM-1 expression on macrophages is mediated, at least partly, by endogenous PGE(2) followed by EP4 and cAMP, protein kinase A, p38 MAPK, and PI3K-mediated signaling. Regulation of TREM-1 and the soluble form of TREM-1 expression by PGE(2) may modulate the inflammatory response to microbial pathogens.

Animals↗
PubMed2006

Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) up-regulation.

Lipoxin A(4) (LXA(4)) is an eicosanoid which is produced via lipoxygenases and characteristic of its anti-inflammatory effect in many metabolites of arachidonic acid, which are mostly pro-inflammatory. Glucocorticoids are well known also for their strong anti-inflammatory action but induce 5-lipoxygenase, essential to synthesize leukotrienes, which are pro-inflammatory. To elucidate the interaction of glucocorticoids and lipoxin A(4) for anti-inflammation, we analyzed in vitro expression of lipoxin A(4) receptor (ALX) on human neutrophils and the in vivo anti-inflammatory effect of glucocorticoids and LXA(4) using a dermal inflammation mouse model. ALX mRNA was up-regulated by dexamethasone (Dex) in human neutrophils. A glucocorticoid receptor antagonist, mifepristone, suppressed up-regulation of ALX induced by Dex. LXA(4) and/or Dex decreased CD11b expression on human neutrophils and suppressed mouse dermatitis induced by LTB(4). These results suggest that anti-inflammatory effects of glucocorticoids depend at least partly on up-regulation of ALX and that the lipoxin system could be a negative feedback regulator for LTB(4).

Adult↗
PubMed2006

Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals.

OBJECTIVE: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM-1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM-1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM-1 expression by MSU crystal-stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation was determined. The biologic role of TREM-1 in crystal-induced cytokine production by resident peritoneal macrophages was also investigated. METHODS: TREM-1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model was determined by quantitative real-time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti-TREM-1 agonist antibody was determined by enzyme-linked immunosorbent assay. RESULTS: TREM-1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM-1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti-TREM-1 agonist antibody synergistically increased the production of both interleukin-1beta and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM-1 expression in infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation. CONCLUSION: These findings suggest that rapid induction of TREM-1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses.

Acute Disease↗
PubMed2005

Inhibition of skin sclerosis by 15deoxy delta12,14-prostaglandin J2 and retrovirally transfected prostaglandin D synthase in a mouse model of bleomycin-induced scleroderma.

Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme involved in production of the PGD and J series, which have various role in inflammation and immunity. We evaluated the effect of treatment with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) or the injection of prostaglandin D(2) synthase (PGDS) cDNA expressing-retrovirally transfected fibroblasts on bleomycin (BLM)-induced scleroderma-like skin sclerosis. Daily injection of BLM (30 microg) for 4 weeks induced histological evidence of dermal sclerosis in C3H mice. We examined the effect of injection of 15d-PGJ(2) (30 ng twice a day) or PGDS expressing-retrovirally transfected fibroblast on BLM-induced dermal sclerosis. Administration of 15d-PGJ(2) (a nonenzymatic metabolite of PGD(2)) injection of PGDS cDNA-expressing fibroblasts significantly reduced dermal sclerosis, the hydroxyproline content, and dermal thickness. Moreover, 15-d PGJ2 down-regulation of the expression of transforming growth factor beta(1) and connective tissue growth factor which had been induced by BLM. Mast cells were also increased in the skin by BLM injection and there was prominent degranulation of these mast cells along with elevated plasma histamine levels. 15-d PGJ(2) and PGDS-expressing cells also suppressed degranulation of cultured mast cells and histamine release by these cells. These results show that 15-d PGJ(2) and PGDS-expressing cells can prevent experimental skin sclerosis induced by BLM and raise the possibility of therapeutic approaches targeting of PPARgamma for the skin lesion of scleroderma.

Animals↗
PubMed2004

Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts.

BACKGROUND: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide (a constituent of TWHF) could influence the proliferation of rheumatoid synovial fibroblasts (RSF) by induction of apoptosis. RESULTS: RSF were obtained from RA patients during surgery and were treated with triptolide under various conditions. The viability and proliferation of RSF were measured by the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay and by 5-bromo-2'-deoxyuridine incorporation, respectively. Apoptosis was identified by detection of DNA fragmentation using an enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). The role of caspases in apoptosis of RSF was analyzed by measuring caspase-3 activity. Activation of the peroxisome proliferator-activated receptor (PPAR) gamma was assessed by a luciferase reporter gene assay using RSF transfected with a plasmid containing the peroxisome proliferator response element. Triptolide decreased viability, inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low (nM) concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors. Although PPARgamma activation was induced by 15-deoxy-Delta12,14-prostaglandin J2, triptolide did not induce it under the same experimental conditions. An extract of TWHF also induced DNA fragmentation in RSF. CONCLUSION: The mechanism of action remains to be studied; however, triptolide may possibly have a disease-modifying effect in patients with RA.

Apoptosis↗
PubMed2004

[Disinfection of water of remove Legionella species: evaluation of an antimicrobial ceramic].

To evaluate the efficacy of an antimicrobial ceramic for killing Legionella strains in vitro, bacteria were exposed to the ceramic soaked in PBS at 25 degrees C or 42 degrees C. The number of L. pneumophila began to decrease significantly after 4 h of exposure at 25 degrees C and reached < 10 log cfu/ml after 12 h. A similar significant decrease was also observed after exposure at 42 degrees C. Furthermore, it was found that the antimicrobial ceramic showed bactericidal activity against six strains of Legionella isolated from various water sources, including L. pneumophila (serotype 1-4), L. micdadei, and L. dumoffii, after 24 h of exposure. The antimicrobial activity against L. pneumophila of the supernatant obtained by soaking the ceramic in PBS for 24 h was also assessed. Bactericidal activity of this supernatant was also noted. Analysis of the supernatant by ICP-MS resulted in the detection of eight metals (Mg, Al, Ca, Mn, Zn, Sr, Ag, and Ba) at a maximum concentration of 2.5 mg/l. When reconstituted PBS was made with all eight metals at the same concentrations as in the supernatant, the reconstituted PBS containing Ag alone and all metals showed significantly bactericidal activity against L. pneumophila, but PBS with only one metal component except Ag or a combination of Ag with Zn and/or Ca did not. These findings suggest that the antimicrobial ceramic possesses strong bactericidal activity against Legionella species and that eight metals released from the ceramic have a synergistic bactericidal effect against Legionella. When the antimicrobial ceramic was placed in hot spring water or cooling tower water instead of PBS, the number of L. pneumophila in the water decreased to < 10 log cfu/ml after 24 h of exposure and the bactericidal activity persisted for 5 weeks. These results indicate that the antimicrobial ceramic can be used to eradicate Legionella species contaminating various water sources.

Ceramics↗
PubMed2003

Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth.

Nonsteroidal antiinflammatories are known to suppress incidence and progression of malignancies including colorectal cancers. However, the precise mechanism of this action remains unknown. Using prostaglandin (PG) receptor knockout mice, we have evaluated a role of PGs in tumor-associated angiogenesis and tumor growth, and identified PG receptors involved. Sarcoma-180 cells implanted in wild-type (WT) mice formed a tumor with extensive angiogenesis, which was greatly suppressed by specific inhibitors for cyclooxygenase (COX)-2 but not for COX-1. Angiogenesis in sponge implantation model, which can mimic tumor-stromal angiogenesis, was markedly suppressed in mice lacking EP3 (EP3(-/-)) with reduced expression of vascular endothelial growth factor (VEGF) around the sponge implants. Further, implanted tumor growth (sarcoma-180, Lewis lung carcinoma) was markedly suppressed in EP3(-/-), in which tumor-associated angiogenesis was also reduced. Immunohistochemical analysis revealed that major VEGF-expressing cells in the stroma were CD3/Mac-1 double-negative fibroblasts, and that VEGF-expression in the stroma was markedly reduced in EP3(-/-), compared with WT. Application of an EP3 receptor antagonist inhibited tumor growth and angiogenesis in WT, but not in EP3(-/-). These results demonstrate significance of host stromal PGE(2)-EP3 receptor signaling in tumor development and angiogenesis. An EP3 receptor antagonist may be a candidate of chemopreventive agents effective for malignant tumors.

Animals↗
PubMed2003

Rapid induction of peroxisome proliferator-activated receptor gamma expression in human monocytes by monosodium urate monohydrate crystals.

OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR gamma in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPAR gamma expression by monosodium urate monohydrate (MSU) crystal-stimulated monocytes, and we studied the effects of PPAR gamma ligands on crystal-induced acute inflammation. METHODS: PPAR gamma expression by MSU crystal-stimulated human peripheral blood mononuclear cells was determined by reverse transcription-polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR gamma ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated. RESULTS: MSU crystals rapidly and selectively induced PPAR gamma expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR gamma was functional, since a PPAR gamma ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPAR gamma, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15deoxy-PGJ(2)), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ(2) significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal-induced acute inflammation. CONCLUSION: Rapid induction of PPAR gamma expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.

Acute Disease↗
PubMed2003

Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase.

OBJECTIVE: Hematopoietic prostaglandin D synthase (H-PGDS) is a key enzyme in the production of prostaglandin D and its J series metabolites. We evaluated the antiinflammatory effect of retrovirally transfected H-PGDS in order to investigate the role of H-PGDS in monosodium urate monohydrate (MSU) crystal-induced acute inflammation. METHODS: Expression of endogenous PGDS in a murine air-pouch model of MSU crystal-induced acute inflammation was determined by real-time polymerase chain reaction. H-PGDS complementary DNA (cDNA) was retrovirally transfected into C57BL/6J fibroblasts, and the cells were designated as C57-PGDS cells. Production of prostaglandins by C57-PGDS cells was measured by enzyme immunoassay. The effect of C57-PGDS cells on crystal-induced inflammation was investigated. RESULTS: Injection of the crystals caused a rapid decrease in H-PGDS expression by infiltrating cells and by the soft tissues around the air pouches. In contrast, expression of interleukin-1beta (IL-1beta) and macrophage inflammatory protein 2 (MIP-2) as well as cellular infiltration were significantly increased during the early stage of inflammation. C57-PGDS cells, but not control cells, produced an increased amount of PGD(2) in vitro, but suppressed production of PGE(2). Injection of C57-PGDS cells into air pouches inhibited cellular infiltration and MIP-2 and IL-1beta expression. CONCLUSION: In this murine air-pouch model of MSU crystal-induced inflammation, retrovirally transfected H-PGDS cDNA could reduce cellular infiltration, at least partly by inhibiting MIP-2 and IL-1beta. These findings suggest that gene therapy with H-PGDS may be useful for treating inflammatory diseases.

Acute Disease↗
PubMed2003

Apoptosis of intestinal crypt epithelium after Cryptosporidium parvum infection.

Using a neonatal mouse model of Cryptosporidium parvum infection, we investigated whether apoptosis of epithelial cells was induced in the small intestine. At the time when the number of C. parvum oocysts in the ileum was maximal, columnar goblet cells and absorptive cells showed a decrease in the ileal epithelium that was accompanied by a significant reduction in the height of the villi. A few apoptotic epithelial cells were also observed in the vicinity of the basal crypts where C. parvum was proliferating. Morphological changes of the villous structure and apoptotic epithelial cells associated with proliferation of the parasite were scarcely detected in the duodenum, cecum, and colon of the infected mice. These findings suggest that the loss of absorptive cells and goblet cells, and the apoptosis of intestinal epithelial cells, are common events in the ileum after C. parvum infection, and that epithelial apoptosis may have a significant role in the pathogenesis of cryptosporidiosis.

Animals↗
PubMed2003

Pretreatment of Pseudomonas aeruginosa with a sub-MIC of imipenem enhances bactericidal activity of neutrophils.

The influence of the pretreatment of Pseudomonas aeruginosa strain O1 (PAO-1) with a sub-minimum inhibitory concentration (MIC) of imipenem on bactericidal activity, phagocytosis, the production of oxygen radical intermediates, and the induction of apoptosis in murine peritoneal neutrophils, as well as the catalase activity in the bacteria in comparison with that of ceftazidime-treated bacteria were studied. Bacteria treated with imipenem at (1/4) MIC were killed at significantly higher rates by neutrophils than ceftazidime-treated and nontreated bacteria. However, antibiotic-treated bacteria showed similar numbers of bacteria-phagocytized neutrophils to those in untreated bacteria. Imipenem pretreatment of bacteria led to an increase in the production of oxygen radical intermediates by neutrophils and the inhibition of neutrophilic apoptosis following incubation, whereas these features did not occur in neutrophils incubated with nontreated and ceftazidime-treated bacteria. The catalase activity of bacteria was not suppressed by pretreatment with either antibiotic at (1/4) MIC. These findings suggest that the exposure of P. aeruginosa to a sub-MIC of imipenem enhances the susceptibility of the bacteria to neutrophilic killing and effectively modifies the physiological activities of neutrophils, but does not decrease bacterial catalase activity. These actions may account for the postantibiotic leukocyte enhancement (PALE) effect of a sub-MIC of imipenem in the host.

Animals↗
PubMed2003

COX-2/VEGF-dependent facilitation of tumor-associated angiogenesis and tumor growth in vivo.

Nonsteroidal anti-inflammatory drugs are known to suppress the occurrence and progression of malignancies such as colorectal cancers. However, the precise mechanism of these actions remains unknown. We have evaluated the role of an inducible cyclo-oxygenase (COX-2) in tumor-associated angiogenesis and tumor growth, and identified the downstream molecules involved using a ddy mouse model of sponge angiogenesis, which mimics tumor angiogenesis and is COX-2 and vascular endothelial growth factor (VEGF) dependent. In this model, VEGF expression was down-regulated by selective COX-2 inhibition with NS-398. To find out the involvement of COX-2/VEGF pathway in tumor-associated angiogenesis, we estimated angiogenesis occurring around implanted Millipore chambers containing sarcoma-180 (S-180) cells or Lewis lung carcinoma cells. Daily oral administration of NS-398 or of aspirin, a nonselective COX inhibitor, suppressed angiogenesis seen around the Millipore chambers. S-180 cells implanted in ddy mice formed substantial tumors with extensive angiogenesis markedly suppressed by aspirin and COX-2 inhibitors NS-398 and JTE522, but not by mofezolac, an inhibitor of constitutive COX-1. Tumor-associated angiogenesis was also significantly suppressed by a neutralizing antibody against VEGF. S-180 tumor growth in the subcutaneous tissues was also suppressed by aspirin, COX-2 selective inhibitors, and the VEGF antibody, but not by the COX-1 inhibitor. These results demonstrate that the inhibition of the COX-2/VEGF-dependent pathway was effective in tumor-associated angiogenesis, tumor growth, and tumor metastasis.

Animals↗
PubMed2003

[Effect of the mixed-oxidant solution on infectivity of Cryptosporidium parvum oocysts in a neonatal mouse model].

Cryptosporidium parvum oocysts were exposed to the mixed-oxidant solution, which was electrochemically generated by Miox Water Disinfection Unit, and sodium hypochlorite in phosphate buffered saline (PBS, pH 7.2) or biologically treated wastewater at 25 degrees by using concentrations of residual chlorine of up to 5 mg/l and contact times of up to 8 h. The effect of two disinfectants on infectivity of the oocysts in a neonatal murine model was comparatively evaluated by determining the total number of oocysts recovered from the intestine. Exposure to the mixed-oxidant solution at 2 and 5 mg/l (residual chlorine) yielded a significant inactivation of infectivity in the dose- and exposure time-dependent manner, while exposure to 5 mg/l (residual chlorine) of sodium hypochlorite for contact times of up to 4 h produced no measurable inactivation of infectivity. Morphological examination also revealed a picture of degenerating oocysts after exposure to 5 mg/l (residual chlorine) of the mixed-oxidant solution, but not with sodium hypochlorite. When the oocysts were exposed to either biologically treated wastewater--or PBS-diluted the mixed-oxidant solution at 5 mg/l (residual chlorine) for 4 h, the disinfectants produced a significant inactivation of infectious oocysts. The decrease number of the oocysts was 0.8 log 10 in the former and 2.1 log 10 in the latter. These results demonstrate that the mixed-oxidant solution may be a useful disinfectant against Cryptosporidium oocysts, but appropriate applications need to be validated.

Animals↗
PubMed2003

Production of macrophage inflammatory protein 3alpha (MIP-3alpha) (CCL20) and MIP-3beta (CCL19) by human peripheral blood neutrophils in response to microbial pathogens.

Effects of bacterial pathogens on the production of macrophage inflammatory protein 3alpha (MIP-3alpha) and MIP-3beta from human peripheral blood neutrophils were investigated. Neutrophils produced both chemokines by coincubation with either gram-positive or gram-negative bacteria. Neutrophils may initiate antigen-specific immune responses through the release of these chemokines that are capable of promoting selective recruitment of dendritic cells and T-cell subsets.

Chemokine CCL20↗
PubMed2003

Detection of human papillomavirus type 57 in the tissue of a plantar epidermoid cyst.

Plantar epidermoid cysts with human papillomavirus (HPV) infection are not rare in Japan. Most of them show the cytopathic effect of HPV type 60 - homogeneous intracytoplasmic inclusion bodies. Our case presented a plantar epidermoid cyst with vacuolation around the granular cell layer without any features of HPV type 60. In situ hybridization and polymerase chain reaction followed by DNA sequencing analysis revealed an association with HPV type 57.

Adult↗
PubMed2003

Retrovirally introduced prostaglandin D2 synthase suppresses lung injury induced by bleomycin.

Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme to produce prostaglandin (PG) D and J series. These PGs are involved in inflammation and immune system. The PGDS complementary DNA (cDNA)-expressing retrovirally transfected fibroblasts were introduced in vivo, and effect of the expression on lung injury induced by bleomycin was investigated in mice. Intravenous injection of PGDS cDNA-expressing fibroblasts significantly reduced lung edema, leukocyte infiltration in bronchoalveolar lavage (BAL) fluid, and pulmonary collagen content at 4 wk after instillation of bleomycin. Survival rate in mice instilled with the PGDS-expressing fibroblasts was higher than that in mice that received the mock transfection. Administration of 15-deoxy-Delta 12,14-PGJ2, which is a nonenzymatic metabolite of PGD2, also attenuated the lung injury, suggesting mediation of PGs produced by PGDS for the attenuation. Introduction of PGDS cDNA-expressing fibroblasts suppressed expression of basic fibroblast growth factor, connective tissue growth factor, and collagen messenger RNAs in the lungs, as well as the levels of total proteins and hemoglobin in BAL fluid. These data suggest that the suppressive effect of PGDS on the lung injury could be partly mediated by edema formation and inhibition of genes involved in the fibrotic change.

Animals↗
PubMed2003

Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synovial tissues and synovial fluid leukocytes of patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the role of leukotriene B4 (LTB4) receptors in inflammatory arthritis, we investigated the expression of BLT1 and BLT2 mRNA in synovial tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. BLT1 and BLT2 mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization in synovial tissues from 40 patients with RA and 10 patients with OA. Results. BLT2 (the low-affinity receptor for LTB4) showed stronger expression than BLT1 (the high-affinity receptor) in actively inflamed synovial tissue from patients with RA. Synovial macrophages, fibroblast-like cells, and lymphocytes expressed BLT2 mRNA in RA synovial tissues showing active inflammation. BLT2 mRNA was strongly expressed in the synovial lining cells, which also expressed 5-lipoxygenase, an enzyme that synthesizes LTB4. BLT1 and BLT2 mRNA expression in synovial tissues was stronger in RA than in OA by real-time quantitative PCR. In contrast, leukocytes infiltrating synovial fluid predominantly expressed BLT1 mRNA in patients with RA. It was recently reported that these 2 receptors for LTB4 have quite different pharmacological effects and a different tissue distribution. Conclusion. BLT2 is the main receptor mediating the effects of LTB4 in the synovial tissues of patients with RA; this suggests the possibility of developing a new therapy to block LTB4 in inflammatory arthritis.

Aged↗