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Updated: Mar 31, 2026
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Published on: February 10, 2021
C5a and toll-like receptor 4 crosstalk in retinal pigment epithelial cells
Yi Zhu1, Bingling Dai2, Yongguo Li3
1The People's Hospital of Kai County, Chongqing, China.
Purpose:
To investigate the effect of the complement activation product C5a on toll-like receptor (TLR) 4-induced responses in RPE cells.
Methods:
Confluent cultures of human RPE cells (ARPE-19) were stimulated with C5a, lipopolysaccharide (LPS), or a combination of the two. The expression of TLR4 was determined by real-time PCR and flow cytometry. Cytokine profiles were determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). The phosphorylation of p38, ERK 1/2, and JNK was measured by flow cytometry.
Results:
C5a stimulation enhanced the expression of TLR4 in a dose- and time-dependent manner. C5a was able to stimulate the production of TLR4-induced IL-6 and IL-8 by ARPE-19 cells. Blocking experiments showed that the effect of C5a on cytokine production was mediated via C5aR. ERK1/2, but not JNK or p38, were involved in the production of IL-6 and IL-8.
Conclusions:
The results indicate that C5a can induce the TLR4 expression and enhance the production of TLR4-induced IL-6 and IL-8 by ARPE-19. The effect of C5a on cytokine production was mediated by C5aR and the phosphorylation of ERK1/2.
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