Antagonistic effects of activin A and TNF-\u03b1 on the activation of L929 fibroblast cells via Smad3-independent signaling

Zhonghui Liu,Xueling Cui,Linru Zhu,Yan Qi,Boyang Liu,Lingling Jiang

doi:10.1038/s41598-020-77783-8

Zhonghui Liu, Xueling Cui + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-77783-8

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Abstract

Fibroblasts play an important role in inflammation and tissue fibrosis. Both activin A and TNF-α can activate immune cells, however, the roles and relationship of them in activating fibroblasts in inflammation remain unclear. Here, this study revealed that TNF-α promoted the release of NO and IL-6 by L929 fibroblast cells, but co-treatment with activin A attenuated these effects. In contrast, activin A induced cell migration and increased the production of tissue fibrosis-related TGF-β1 and fibronectin, while TNF-α inhibited these function changes of L929 cells induced by activin A. Moreover, this study revealed that activin A and TNF-α regulated the activities of L929 cells via ERK1/2/MAPK pathway, rather than Smad3-dependent signaling pathway. Taken together, these data indicate that activin A and TNF-α exert mutually antagonistic effects on regulating fibroblasts activities, and the balance between their action may determine the process and outcome of fibroblasts-mediated inflammation.

Highlights

Fibroblasts, which are the main cells in loose connective tissue, are the major functional cells during wound healing, and are involved in the regulation of immune response[1]
Activin A had no significant effect on nitric oxide (NO) release by L929 cells, but it inhibited NO secretion by TNF-α-activated L929 cells (Fig. 1a)
TNF-α significantly up-regulated the expression of iNOS mRNA, while activin A had no significant effect on the expression of iNOS mRNA in L929 cells (Fig. 1b)

Summary

Introduction

Fibroblasts, which are the main cells in loose connective tissue, are the major functional cells during wound healing, and are involved in the regulation of immune response[1]. Fibroblasts exert diverse biological roles in different stages of tissue injury. It has been reported that activin A exerts anti-inflammatory roles in the early inflammation, and participates in tissue repair and fibrosis in the late inflammation[10,11]. Both activin A and TNF-α can activate immune cells to participate in immune response, what role TNF-α plays in the process of tissue repair and fibrosis and how it is related to and different from activin A in activating fibroblasts are still unclear. We took murine fibroblast cell line L929 as the object to investigate the biological effects of activin A and TNF-α on fibroblasts and the interaction between them in fibroblasts-mediated inflammation

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Results

Conclusion