Sarcoid-like granulomatosis induced by Propionibacterium acnes in mice; role of ICAM-1 in prevention of granuloma formation

Abstract

Sarcoidosis is a systemic granulomatous disease which is characterized by a variable clinical presentation and course. The etiology of the disease has remained unknown. Propionibacterium acnes (P. acnes), an anaerobic nonspore-forming gram-positive rod bacterium, has been implicated as one of the suggested causative antigens of sarcoidosis since this bacterium has been isolated from sarcoid lesions. In order to clarify the role of cell adhesion molecules in cutaneous sarcoidosis, we first established an in vivo model of sarcoid-like skin granulomatosis by injecting heat-killed P. acnes into the back of C57BL/6 J mice. These mice injected with P. acnes on days 1, 3, 5, and 14 showed prominent sarcoid-like granulomatosis not only in the skin but also in the lung at day 28. Next, we investigated the role of inter-cellular adhesion molecule(ICAM)-1, L-selectin, P-selectin and E-selectin in the formation of granuloma, using mice lacking each of these molecules. We injected heat-killed P.acnes into the back of these deficient mice as described above. Histopathological findings revealed that granuloma formation was aggravated in the lung and the skin of ICAM-1-deficient mice, compared to those of wild type mice. Real-time polymerase chain reaction assay demonstrated increased tumor necrosis factor-alpha mRNA expression in both skin and lungs of ICAM-1 deficient mice. In contrast, interleukin-10 mRNA expression was not detected in the skin of ICAM-1 deficient mice, while it was increased in that of wild type. Our results indicate that ICAM-1 is imperative to produce interleukin-10, which is necessary to prevent granuloma formation in the skin. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF