{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:17:04Z","timestamp":1792199824414,"version":"4.4.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,3,1]]},"abstract":"<jats:p>CD40 is an important signaling and activation antigen found on certain bone marrow-derived cells. Recently, CD40 has also been shown to be expressed by nonhematopoietic cells, including certain human fibroblasts, but not others. Little is known about the function of CD40 on fibroblasts. The current study investigates the hypothesis that CD40 is expressed on orbital fibroblasts and represents a pathway for interaction between these fibroblasts and CD40 ligand-expressing cells, such as T lymphocytes and mast cells. We report here that orbital connective tissue fibroblasts, obtained from normal donors and from patients with severe thyroid-associated ophthalmopathy (TAO), express functional CD40. CD40 is upregulated \u223c10-fold by interferon-\u03b3 (500 U\/ml) treatment for 72 h. These fibroblasts become activated through triggering of CD40 with CD40 ligand (CD40L). This is evidenced by nuclear translocation of nuclear factor-\u03baB and induction of the proinflammatory and chemoattractant cytokines interleukin-6 and interleukin-8, respectively. These data support the concept that cognate interactions between orbital fibroblasts and infiltrating T lymphocytes, via the CD40-CD40L pathway, may promote the tissue remodeling observed in TAO and other inflammatory diseases of the orbit. Disruption of the CD40-CD40L interaction may represent a therapeutic intervention to reduce the inflammatory components of TAO, which remains a vexing clinical problem.<\/jats:p>","DOI":"10.1152\/ajpcell.1998.274.3.c707","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T11:46:05Z","timestamp":1514115965000},"page":"C707-C714","source":"Crossref","is-referenced-by-count":123,"title":["Human orbital fibroblasts are activated through CD40  to induce proinflammatory cytokine production"],"prefix":"10.1152","volume":"274","author":[{"given":"Gregory D.","family":"Sempowski","sequence":"first","affiliation":[{"name":"University of Rochester Cancer Center and Departments of Microbiology and Immunology, Pediatrics, and Environmental Medicine, University of Rochester, Rochester 14642; Division of Molecular and Cellular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, Albany Medical College, and Samuel S. 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