AXL Inhibits Proinflammatory Factors to Relieve Rheumatoid Arthritis Pain by Regulating the TLR4/NF-κB Signaling Pathway

Abstract

Objective. This study aims to explore the role and mechanism of AXL receptor tyrosine kinase (AXL) in relieving inflammatory pain caused by rheumatoid arthritis (RA). Methods. RA mouse model was constructed by collagen antibody induction. RT-qPCR and Western blot were used to detect the level of AXL in RA fibroblast-like synovial cells (RA-FLS) and joint synovium. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were detected by ELISA. The inflammatory infiltration in joints was determined via HE staining. The mechanical abnormal pain and hyperalgesia were detected by the Von Frey microfilament test. The protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (3COX-2), toll-like receptor 4 (TLR4), p65, and phosphor (p)-p65 were detected by Western blotting. Results. The expression of AXL in RA-FLS and RA mice was downregulated, while the expression of iNOS and COX-2 was upregulated. The levels of inflammatory cytokines IL-6, TNF-α, and NO were increased in RA-FLS and RA mice. RA mice presented inflammatory cell infiltration, bone and cartilage destruction, and joint space stenosis. AXL overexpression alleviated inflammatory cell infiltration, inflammatory cytokine secretion, and pathological injury in RA mice. Additionally, AXL overexpression inhibited the expression of TLR4 and p-p65. Conclusion. AXL inhibits inflammatory pain in RA mice by suppressing TLR4/NF-κB pathway.

LncRNA HOTTIP regulates TLR4 promoter methylation by recruiting H3K4 methyltransferase MLL1 to affect apoptosis and inflammatory response of fibroblast‐like synoviocyte in rheumatoid arthritis

“…Slices, 6 μm thick, were prepared at a 5° angle to the paraffin surface, followed by 5‐min each soak in 100%, 95%, 85%, and 75% graded ethanol, and 5‐min staining with hematoxylin and 2‐min eosin staining to assess joint pathology. Joint pathology was assessed by inflammation degree, conducted by three experts on a scale from 0 to 4: 0, no inflammation; 1 to 2, mild inflammation; 3, moderate inflammation; and 4, severe inflammation 14 …”

“…Joint pathology was assessed by inflammation degree, conducted by three experts on a scale from 0 to 4: 0, no inflammation; 1 to 2, mild inflammation; 3, moderate inflammation; and 4, severe inflammation. 14 2.6 | Tartrate-resistant acid phosphatase (TRAP) staining…”

Apoptotic cell clearance components in inflammatory arthritis

“…These data implicate MERTK as a critical efferocytosis receptor in mouse models of RA. Role of AXL in efferocytosis in arthritic joints is less clear, though evidence of its protective role is also shown in the CAIA model by reduced inflammation of the joints injected with lentiviral Axl expression vectors 49 . TYRO3, on the other hand, contributes to synovial hyperplasia and osteoclast activation in K/BxN serum‐induced arthritis, as Tyro3 −/− mice display reduced joint inflammation and bone erosion 50 .…”

“…Role of AXL in efferocytosis in arthritic joints is less clear, though evidence of its protective role is also shown in the CAIA model by reduced inflammation of the joints injected with lentiviral Axl expression vectors. 49 TYRO3, on the other hand, contributes to synovial hyperplasia and osteoclast activation in K/BxN serum-induced arthritis, as Tyro3 −/− mice display reduced joint inflammation and bone erosion. 50 Collectively, these studies suggest non-overlapping functions of different PtdSer receptors in inflammatory arthritis.…”

Retracted: AXL Inhibits Proinflammatory Factors to Relieve Rheumatoid Arthritis Pain by Regulating the TLR4/NF‐κB Signaling Pathway

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”