Effect of interleukin-4 on the synthesis of the third component of complement by pulmonary epithelial cells.
Complement activation in the lung is important in a variety of physiological and pathological conditions. The third component of complement, C3, is the pivotal constituent of the complement cascade. C3 is produced in the lung by several cell types including pulmonary epithelial cells. Because pulmonary epithelial cells and T lymphocytes may interact within the lung to regulate local immune responses, we examined the effect of a T lymphocyte-derived cytokine, interleukin-4 (IL-4) on C3 production by A549 human pulmonary epithelial cells. Treatment of A549 cells with IL-4 increased C3 production in a time- and dose-dependent fashion. Concentrations of IL-4 > or = 0.1 ng/ml significantly increased C3 production. Maximal increase in C3 synthesis occurred after stimulation of A549 cells with IL-4 (10 ng/ml) for 3 days. Preincubation of IL-4 with a neutralizing anti-human IL-4 antibody inhibited IL-4's effect on C3 production. The relative abundance of C3 messenger RNA levels in A549 cells increased following IL-4 treatment, indicating that IL-4's effects on C3 production were pretranslational. Intercellular communication between T lymphocytes and pulmonary epithelial cells via cytokines such as IL-4 may be important in the local regulation of C3 gene expression during the inflammatory response.
Christian-Ritter
K K
KK
Department of Pediatrics, Creighton University, Omaha, Nebraska.
Hill
L D
LD
Hoie
E B
EB
Zach
T L
TL
D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D003176:Complement C3; D012333:RNA, Messenger; D015847:Interleukin-4