METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway
Methyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mec...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/3120391 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556964774674432 |
|---|---|
| author | Jinghua Wang Shushan Yan Hongying Lu Shufeng Wang Donghua Xu |
| author_facet | Jinghua Wang Shushan Yan Hongying Lu Shufeng Wang Donghua Xu |
| author_sort | Jinghua Wang |
| collection | DOAJ |
| description | Methyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mechanism of METTL3 in rheumatoid arthritis (RA). The aim of the present study is to elucidate the function and potential mechanism of METTL3 in RA pathogenesis. We used quantitative real-time polymerase chain reaction to detect the expression of METTL3 in RA patients and controls as well as the macrophage cell line. CCK-8 was used for cell proliferation assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to estimate the generation of IL-6 and TNF-α in macrophages. Western blot and immunofluorescence were applied to evaluate the activation of NF-κB in macrophages. The expression of METTL3 was significantly elevated in patients with RA. It was positively associated with CRP and ESR, two common markers for RA disease activity. Besides, LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages. Moreover, the effect of METTL3 on LPS-induced inflammation in macrophages was dependent on NF-κB. This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA. |
| format | Article |
| id | doaj-art-923a69eb6dc84acdb4c3e4360a4d9c52 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-923a69eb6dc84acdb4c3e4360a4d9c522025-02-03T05:43:55ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/31203913120391METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling PathwayJinghua Wang0Shushan Yan1Hongying Lu2Shufeng Wang3Donghua Xu4Clinical Medicine College, Weifang Medical University, Weifang 261000, ChinaDepartment of Gastrointestinal and Anal Diseases Surgery, The Affiliated Hospital of Weifang Medical University, Weifang 261000, ChinaFunctional Laboratory, Clinical Medicine College, Weifang Medical University, Weifang 261000, ChinaMedical Experimental Training Center, Weifang Medical University, Weifang 261000, ChinaClinical Medicine College, Weifang Medical University, Weifang 261000, ChinaMethyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mechanism of METTL3 in rheumatoid arthritis (RA). The aim of the present study is to elucidate the function and potential mechanism of METTL3 in RA pathogenesis. We used quantitative real-time polymerase chain reaction to detect the expression of METTL3 in RA patients and controls as well as the macrophage cell line. CCK-8 was used for cell proliferation assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to estimate the generation of IL-6 and TNF-α in macrophages. Western blot and immunofluorescence were applied to evaluate the activation of NF-κB in macrophages. The expression of METTL3 was significantly elevated in patients with RA. It was positively associated with CRP and ESR, two common markers for RA disease activity. Besides, LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages. Moreover, the effect of METTL3 on LPS-induced inflammation in macrophages was dependent on NF-κB. This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.http://dx.doi.org/10.1155/2019/3120391 |
| spellingShingle | Jinghua Wang Shushan Yan Hongying Lu Shufeng Wang Donghua Xu METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway Mediators of Inflammation |
| title | METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway |
| title_full | METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway |
| title_fullStr | METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway |
| title_full_unstemmed | METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway |
| title_short | METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway |
| title_sort | mettl3 attenuates lps induced inflammatory response in macrophages via nf κb signaling pathway |
| url | http://dx.doi.org/10.1155/2019/3120391 |
| work_keys_str_mv | AT jinghuawang mettl3attenuateslpsinducedinflammatoryresponseinmacrophagesvianfkbsignalingpathway AT shushanyan mettl3attenuateslpsinducedinflammatoryresponseinmacrophagesvianfkbsignalingpathway AT hongyinglu mettl3attenuateslpsinducedinflammatoryresponseinmacrophagesvianfkbsignalingpathway AT shufengwang mettl3attenuateslpsinducedinflammatoryresponseinmacrophagesvianfkbsignalingpathway AT donghuaxu mettl3attenuateslpsinducedinflammatoryresponseinmacrophagesvianfkbsignalingpathway |