In situ expression of transforming growth factor beta in streptococcal cell wall-induced granulomatous inflammation and hepatic fibrosis.
The expression of transforming growth factor beta (TGF-beta) was examined during the evolution of streptococcal cell wall (SCW)-induced hepatic granulomas in rats to evaluate the role of TGF-beta in chronic inflammation progressing to fibrosis. As determined by immunocytochemistry, Kupffer cells rapidly expressed TGF-beta 1 following intraperitoneal (i.p.) injection of SCW, and TGF-beta was expressed by mononuclear phagocytes in the earliest cell aggregates as well as by mononuclear phagocytes within the capsule of mature lesions. Interestingly, apparent extracellular TGF-beta was observed in mature lesions at the interface of the capsule and the cellular core, a region of active fibrogenesis. Granulomas isolated 3, 6, and 12 weeks post-SCW injection elaborated nanogram (ng) quantities of latent and active TGF-beta into culture supernatants, and expressed high levels of 2.4 and 1.9 kb TGF-beta 1 transcripts. Expression of procollagen type I and III mRNAs were observed in parallel with the expression of the TGF-beta 1 transcripts. Thus, TGF-beta is expressed throughout SCW-granuloma development, and, based on known bioactivities, it appears that TGF-beta mediates, in part, the recruitment and activation of monocytes and fibroblasts and deposition of collagen in SCW-granulomas and likely other chronic inflammatory lesions progressing to fibrosis.
Manthey
C L
CL
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Allen
J B
JB
Ellingsworth
L R
LR
Wahl
S M
SM
D000818:Animals; D015152:Blotting, Northern; D002473:Cell Wall; D002478:Cells, Cultured; D046508:Culture Techniques; D005260:Female; D006099:Granuloma / Q000378:metabolism*; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D012995:Solubility; D013291:Streptococcus; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology
D016212:Transforming Growth Factor beta; D012313:RNA