Abstract
The polarization of macrophages plays a critical role in the pathophysiology of rheumatoid arthritis. The macrophages can have pro-inflammatory M1 polarization and various types of alternative anti-inflammatory M2 polarization. Our preliminary results showed that the CDKN2B-AS1/MIR497/TXNIP axis might regulate macrophages of rheumatoid arthritis patients. Therefore, we hypothesized that this axis regulated the polarization of rheumatoid macrophages. Flow cytometry was used to determine the surface polarization markers in M1 or M2 macrophages from healthy donors and rheumatoid arthritis patients. The QPCR and Western Blotting were used to compare the expression of the CDKN2B-AS1/MIR497/TXNIP axis in these macrophages. We Knocked down and overexpressed the axis in the macrophage cell line MD to test its roles in macrophage polarization. Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed higher levels of CD40 and CD80 and lower levels of CD16, CD163, CD206, and CD200R after polarization, they also expressed higher CDKN2B-AS1, lower MIR497, and higher TXNIP. In macrophages from healthy donors, there was no correlation among CDKN2B-AS1, MIR497, and TXNIP. But in macrophages from patients, there were significant correlations. The CDKN2B-AS1 knockdown, MIR497 mimics suppressed the M1 polarization but promoted the M2 polarization in MD cells, while the MIR497 knockdown and the TXNIP overexpression did the opposite. This study demonstrated that elevated CDKN2B-AS1 in macrophages promotes the M1 polarization and inhibited the M2 polarization of macrophages by the CDKN2B-AS1/ MIR497/TXNIP axis.
Highlights
Rheumatoid arthritis is the most common long-term inflammatory joint disease that results in joints stiffness, swelling, and pain [1]
Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed a higher level of CD40 and CD80 and a lower level of CD16, CD163, CD206, and CD200R after polarization, they expressed higher CDKN2B-AS1, lower MIR497, and higher Thioredoxin-interacting protein (TXNIP)
Our preliminary results showed that CDKN2B-AS1/miR497(MIR497)/TXNIP axis might play a role in macrophages extracted from rheumatoid arthritis patients (These data have been merged into the data of this paper)
Summary
Rheumatoid arthritis is the most common long-term inflammatory joint disease that results in joints stiffness, swelling, and pain [1]. Rheumatoid arthritis is not curable, clinical treatments for rheumatoid arthritis can decrease the inflammatory activities in the joints to relieve pain and inhibit joint damage [3]. Macrophages contribute to the secretion of many pro-inflammatory cytokines and chemokines such as TNF and IL-1β [6]. These pro-inflammatory factors activate many downstream cells and result in joint pain and joint damage [7]. Macrophages contribute to the recruitment of antiinflammatory cytokines such as IL-10 [8] These anti-inflammatory factors can negatively regulate autoimmune activities and protect joint tissue [9]. Specific macrophage polarization surface markers in rheumatoid arthritis have not been identified [13, 14], several studies have reported the inflammatory regulation role of macrophages in rheumatoid arthritis [15]
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