Corticotropin-releasing hormone signaling in synovial tissue from patients with early inflammatory arthritis is mediated by the type 1α corticotropin-releasing hormone receptor

Alice N. McEvoy, Barry Bresnihan, Oliver Fitzgerald, Evelyn P. Murphy

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. Elevated levels of corticotropin-releasing hormone (CRH) 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 CRH at peripheral sites, we examined the expression of known CRH 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 CRH 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 CRH receptor subtype messenger RNA (mRNA) expression in RA, PsA, and normal synovial tissue. In addition, CRH receptor expression was examined in isolated synovial endothelial cells and synoviocytes. Results. Selective up-regulation of CRH receptors in inflamed synovial tissue indicated that CRH functions locally, in an autocrine/paracrine receptor-mediated manner. Immunoreactive CRH receptor type 1 (CRH-R1) was expressed abundantly on vascular endothelial cells and discrete perivascular cell populations, identified as mast cells. In all samples of inflamed synovium studied, CRH-R1α mRNA was detected; however, we were unable to identify CRH-R1β or any CRH-R2 isoforms in samples from the same cohort of patients. CRH receptor subtype expression in separated synovial cell populations revealed a pattern of staining similar to that seen in vivo. In contrast, neither CRH receptor subtype was expressed in normal synovial tissue. Conclusion. Our findings suggest that CRH signaling, via CRH-R1α, may play a role in both the vascular changes and the pathologic mechanisms associated with joint inflammation in human arthritis.

Original languageEnglish
Pages (from-to)1761-1767
Number of pages7
JournalArthritis and Rheumatism
Volume44
Issue number8
DOIs
Publication statusPublished - 2001
Externally publishedYes

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