AI Article Synopsis
- This study explores how the expression of peptidylarginine deiminases (PADIs), specifically PADI2 and PADI4, changes during the differentiation of macrophages and influences inflammatory responses.
- It uses methods like Western blotting and proteomic analyses to assess PADI protein levels and the role of citrullinated proteins, finding that PADI levels rise during differentiation and after LPS stimulation.
- The results reveal that increased PAI-2 expression during macrophage differentiation enhances proinflammatory cytokine secretion, while inhibiting PADI activity can suppress this inflammatory response without altering PADI levels.
Article Abstract
Objective: To investigate the expression of peptidylarginine deiminases (PADIs) during macrophage differentiation and its role in inflammatory responses.
Methods: The protein expression of PADI2, PADI4, and citrullinated histone 3 in U937 cells, differentiated macrophages, and macrophages stimulated with lipopolysaccharides (LPS) were analyzed by Western blotting. Three PADI inhibitors were used for assessing their effects on the secretion of proinflammatory cytokines in macrophages. The differential expressed citrullinated proteins during macrophage differentiation were probed by self-prepared anti-citrullinated protein antibodies, and the reactive bands were sent for proteomic analyses. Transfection studies were conducted to search for the functions of specific proteins. A specific protein was cloned and citrullinated for its protein binding study.
Results: The expression of PADI2 and PADI4 markedly increased during macrophage differentiation, whereas the formation of citrullinated histone 3 increased after stimulated with lipopolysaccharides. Three PADI inhibitors suppressed the LPS mediated proinflammatory cytokines secretion, but did not affect the expression of PADI2 and PADI4. Plasminogen activator inhibitor-2 (PAI-2) was citrullinated during macrophage differentiation. The expression of PAI-2 increased during macrophage differentiation and further increased after stimulated with LPS. Suppressed PAI-2 expression decreased the expression and secretion of proinflammatory cytokines. Decreased PADI2 expression also suppressed the expression of PAI-2 and protein levels of citrullinated PAI-2. The citrullination of PAI-2 inhibited its binding ability to proteasome subunit beta type-1 (PSMB1).
Conclusion: PADI2 and PADI4 protein levels increased during the macrophage differentiation resulting in protein citrullination, including PAI-2. The increased expression of PAI-2 promoted inflammatory response, and the citrullination of PAI-2 impaired its binding to PSMB1. Therefore, protein citrullination could play a critical role in macrophage differentiation and function.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492328 | PMC |
| http://dx.doi.org/10.1186/s13075-019-1896-9 | DOI Listing |
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