
<ArticleTitle>Corticotropin-releasing hormone signaling in synovial tissue from patients with early inflammatory arthritis is mediated by the <prot>type 1 alpha corticotropin-releasing hormone receptor</prot>.</ArticleTitle>
<AbstractText>OBJECTIVE: Elevated levels of <prot>corticotropin-releasing hormone</prot> (<prot>CRH</prot>) are produced locally in inflamed human synovial tissue, and previous observations indicate a role for CRH in the pathogenesis of inflammatory joint disease. To further elucidate the biologic role of <prot>CRH</prot> at peripheral sites, we examined the expression of known <prot>CRH</prot> receptor subtypes in inflamed human synovium and compared the expression patterns in normal synovium. METHODS: Immunohistochemical analysis was used to confirm enhanced expression of specific <prot>CRH</prot> receptor subtypes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovium. Immunofluorescence double-labeling was used to further characterize CRH receptor-expressing cells. Reverse transcriptase-polymerase chain reaction analysis was performed to examine <prot>CRH</prot> receptor subtype messenger RNA (mRNA) expression in RA, PsA, and normal synovial tissue. In addition, <prot>CRH</prot> receptor expression was examined in isolated synovial endothelial cells and synoviocytes. RESULTS: Selective up-regulation of <prot>CRH</prot> receptors in inflamed synovial tissue indicated that <prot>CRH</prot> functions locally, in an autocrine/paracrine receptor-mediated manner. Immunoreactive <prot>CRH receptor type 1</prot> (<prot>CRH-R1</prot>) was expressed abundantly on vascular endothelial cells and discrete perivascular cell populations, identified as mast cells. In all samples of inflamed synovium studied, <prot>CRH-R1alpha</prot> mRNA was detected; however, we were unable to identify <prot>CRH-R1beta</prot> or any CRH-R2 isoforms in samples from the same cohort of, patients. <prot>CRH</prot> receptor subtype expression in separated synovial cell populations revealed a pattern of staining similar to that seen in vivo. In contrast, neither <prot>CRH</prot> receptor subtype was expressed in normal synovial tissue. CONCLUSION: Our findings suggest that <prot>CRH</prot> signaling, via <prot>CRH-R1alpha</prot>, may play a role in both the vascular changes and the pathologic mechanisms associated with joint inflammation in human arthritis.</AbstractText>
