論文 - 詳細
| RRC ID | 86216 |
|---|---|
| 著者 | Wu H, Yuan H, Zhang J, He T, Deng Y, Chen Y, Zhang Y, Chen W, Wu C. |
| タイトル | Helicobacter pylori upregulates PAD4 expression via stabilising HIF-1α to exacerbate rheumatoid arthritis. |
| ジャーナル | Ann Rheum Dis |
| Abstract |
OBJECTIVE:Helicobacter pylori infection has been reported to aggravate rheumatoid arthritis (RA), but the relevant mechanism remains unclear. This study aimed to investigate the underlying pathogenic mechanism of H. pylori infection in the progression of RA. METHODS:The Disease Activity Score (DAS-28) and serum anticitrullinated protein antibody (ACPA) levels were compared between H. pylori-negative and H. pylori-positive patients with RA. MH7A cells were stimulated with polyclonal ACPA purified from the peripheral blood of patients with RA. The citrullination levels were assessed by western blot in GES-1 cells and sera. ChIP, luciferase reporter assays, mass spectrometry and ELISA were applied to explore the molecular mechanism of H. pylori infection in RA progression. RESULTS:The DAS-28 and ACPA levels of patients with RA in the H. pylori-positive group were significantly higher than those in the H. pylori-negative group. Polyclonal ACPA derived from H. pylori-positive patients promoted cell proliferation and induced secretion of IL-6 and IL-8. For the first time, we found that H. pylori infection induces cellular protein citrullination by upregulating protein arginine deiminase type 4 (PAD4). Furthermore, we confirmed a direct functional binding of hypoxia-inducible factor 1α on the PADI4 gene promoter. We demonstrated that PAD4 interacts with and citrullinates keratin 1 (K1), and serum and synovial fluid levels of anti-Cit-K1 antibody were markedly increased in H. pylori-infected patients with RA. CONCLUSION:Our findings reveal a novel mechanism by which H. pylori infection contributes to RA progression. Therapeutic interventions targeting H. pylori may be a viable strategy for the management of RA. |
| 巻・号 | 83(12) |
| ページ | 1666-1676 |
| 公開日 | 2024-11-14 |
| DOI | 10.1136/ard-2023-225306 |
| PII | S0003-4967(24)66569-6 |
| PMID | 39107082 |
| PMC | PMC11671999 |
| MeSH | Adult Anti-Citrullinated Protein Antibodies* / immunology Arthritis, Rheumatoid* / immunology Arthritis, Rheumatoid* / metabolism Arthritis, Rheumatoid* / microbiology Cell Line Citrullination Disease Progression* Female Helicobacter Infections* / complications Helicobacter Infections* / immunology Helicobacter pylori* / immunology Humans Hypoxia-Inducible Factor 1, alpha Subunit* / genetics Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism Male Middle Aged Protein-Arginine Deiminase Type 4* / metabolism Protein-Arginine Deiminases / metabolism Up-Regulation* |
| IF | 16.102 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |