YTHDF1 Negatively Regulates Treponema pallidum-Induced Inflammation in THP-1 Macrophages by Promoting SOCS3 Translation in an m6A-Dependent Manner

Abstract

BackgroundPrevious studies have confirmed that the bacterium Treponema pallidum (TP) or its proteins provide signals to macrophages that induce an inflammatory response; however, little is known about the negative regulation of this macrophage-mediated inflammatory response during syphilis infection or the underlying mechanism. Recent evidence suggests the role of the RNA modification, N6-adenosine methylation (m6A), in regulating the inflammatory response and pathogen-host cell interactions. Therefore, we hypothesized that m6A plays a role in the regulation of the inflammatory response in macrophages exposed to TP.MethodsWe first assessed m6A levels in TP-infected macrophages differentiated from the human monocyte cell line THP-1. The binding and interaction between the m6A “writer” methyltransferase-like 3 (METTL3) or the m6A “reader” YT521-B homology (YTH) domain-containing protein YTHDF1 and the suppressor of cytokine signaling 3 (SOCS3), as a major regulator of the inflammatory response, were explored in differentiated TP-infected THP-1 cells as well as in secondary syphilitic lesions from patients. The mechanisms by which YTHDF1 and SOCS3 regulate the inflammatory response in macrophages were assessed.Results and ConclusionAfter macrophages were stimulated by TP, YTHDF1 was upregulated in the cells. YTHDF1 was also upregulated in the syphilitic lesions compared to adjacent tissue in patients. YTHDF1 recognizes and binds to the m6A methylation site of SOCS3 mRNA, consequently promoting its translation, thereby inhibiting the JAK2/STAT3 pathway, and reducing the secretion of inflammatory factors, which results in anti-inflammatory regulation. This study provides the first demonstration of the role of m6A methylation in the pathological process of syphilis and further offers new insight into the pathogenesis of TP infection.

Factors Analysis of the Compliance Rate of Hypertension Detection Control and Self-Assessment Control in Community Outpatient Clinics

“…Outpatient blood pressure testing can provide reference for doctors to diagnose and treat and provide accurate blood pressure data for patients. The economic cost and time cost of self-measurement of blood pressure at home are lower, and self-monitoring of blood pressure by patients outside medical institutions can effectively help hypertensive patients to quickly understand their blood pressure status in the home environment and prompt patients to take corresponding measures in a timely manner [ 11 – 13 ]. Therefore, the study analyzed the relevant factors of hypertension self-testing and the compliance rate of blood pressure detection and control in community outpatient clinics, in order to provide a reference for improving the blood pressure control compliance rate of hypertensive patients.…”

YTHDF1-TRAF6 pathway regulated neuroinflammation response contributed morphine tolerance and hyperalgesia in periaqueductal gray

“…The m6A reader protein YTHDF1 has been proved to be involved in the in ammatory response. It can not only promote the in ammatory response by regulating the translation of P65 or NLRP3 [41,42], but also inhibit the in ammatory response through SOCS3 [43]. Here, YTHDF1 silencing experiments showed that YTHDF1 could inhibit the secretion of in ammatory factors including TNFα, IL-6, IL-1β and NF-κB in vlPAG, suggesting that YTHDF1 may be one of the key factors regulating the in ammatory response of chronic morphine treatments.…”

Anti-arthritic and toxicological evaluation of ethanolic extract of Alternanthera bettzickiana in rats

“…Histopathological assessment is a benchmark for assessing pathological signs exhibited in simultaneous study in which the architecture of organs of treated rats was normal, toxicological signs were not present, and matches with vehicle rats architecture, showing harmless findings of ABEE with LD50 value more than 2000 mg/kg. Toxic substances are metabolically changed into harmless substances in the liver, which is the principal area for metabolism ( Harizal et al, 2010 ; Li et al, 2022 ). At initial phase signs in hepatocytes are not understandable because of suitability of liver to revive the injurious tissues ( Salawu et al, 2009 ).…”