Cytokine regulation of C3 and C5 production by the human type II pneumocyte cell line, A549.
A growing body of literature suggests that a variety of cell products (e.g., cytokines, C components, etc.) likely play an important role during inflammation and host defense by locally regulating the diverse functions of recruited (i.e., immunologic cells) as well as tissue cells. Previously, a number of investigations have demonstrated the ability of immunologic cells to produce C components in vitro, and further studies have identified a variety of cytokines that can regulate C component production by these cells. Recently, we have demonstrated the ability of lung tissue cells, including epithelial cells and fibroblasts, to synthesize and secrete numerous C components and complement regulatory proteins in vitro. Additionally, we have demonstrated that C component production can be modulated by a variety of factors including endotoxin and serum. In our studies we investigated the effects of specific cytokines, i.e., IL and IFN, on the production of the third (C3) and fifth (C5) C components by the continuous cell line of human type II pneumocytes (A549). Specifically, using sensitive ELISA we demonstrated that A549 pneumocytes exposed to IL-1 alpha, IL-1 beta, or IL-2 induced a dose-dependent, more than twofold, increase in C3 production and a 50% decrease in C5 production when compared to control (untreated) A549 cells. Interestingly, IFN-alpha significantly decreased both C3 and C5 production, i.e., 38 and 71%, respectively, in a dose-dependent manner. IFN-gamma had no effect on C3 production, but significantly decreased C5 production by A549 pneumocytes by 84%. These data not only demonstrate that cytokines have the capability to modulate C3 and C5 production by human type II pneumocytes in vitro, but that C3 and C5 production by these cells can be regulated independently by different cytokines. In vivo, cytokine modulation of C component production by local tissue cells likely plays an important role in the regulation of inflammation and host defense within the lung.
Rothman
B L
BL
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
Despins
A W
AW
Kreutzer
D L
DL
D001685:Biological Factors / Q000494:pharmacology*; D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis*; D003182:Complement C5 / Q000096:biosynthesis*; D016207:Cytokines; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology
D001685:Biological Factors; D003176:Complement C3; D003182:Complement C5; D016207:Cytokines; D007370:Interferon Type I; D007375:Interleukin-1; D007376:Interleukin-2; D007371:Interferon-gamma