Expression of the immunomodulator IL-10 in type I pneumocytes of the rat: alterations of IL-10 expression in radiation-induced lung damage.
Fibrosing alveolitis is a disease with inflammatory, proliferative, and fibrotic components. In different models, it has been shown that the cytokine interleukin-10 (IL-10) plays a conflicting role in inflammation-associated fibrotic processes, inasmuch as it is an anti-inflammatory cytokine but also a TH2 cytokine with inherent pro-fibrotic effects. IL-10 is produced primarily by inflammatory cells. In this report, we show in a rat model of radiation-induced fibrosing alveolitis that IL-10 is also produced by type I alveolar epithelial cells in both normal and fibrotic lungs. The total amount of IL-10 in the lung is increased after irradiation, but type I pneumoyctes contain less IL-10. The R3/1 permanent type I pneumocyte cell line also contains IL-10, which is reduced after irradiation. Whereas in the normal lung, the entire alveolar surface is covered by IL-10-producing pneumocytes, this continuity is interrupted in fibrotic lungs, because type I pneumocytes lack full differentiation and thus full spreading over the alveolar surface. The exposure of the IL-10-negative epithelial basal membrane may allow for an easier attachment of inflammatory cells such as alveolar macrophages. These cells have the potential to act in a pro-inflammatory way by tumor necrosis factor alpha and also in a pro-fibrotic way by activating TH2 cytokines.
Haase
Michael G
MG
OncoRay Center for Radiation Research in Oncology, Medical Faculty, Dresden University of Technology, Dresden, Germany. Michael.Haase@OncoRay.de
Klawitter
Anke
A
Geyer
Peter
P
Baretton
Gustavo B
GB
D000818:Animals; D002460:Cell Line; D005260:Female; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D020545:Respiratory Mucosa / Q000166:cytology
D007155:Immunologic Factors; D016753:Interleukin-10