Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be asso...Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.展开更多
BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice dr...BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.展开更多
基金the National Key Research and Development Program of China (Grant No. SQ2017YFSF090096)National Natural Science Foundation of China (Grant No. 81370855,81770756 and 81300627)+3 种基金Foundation of Science and Technology Department of Sichuan Province (Grant No. 2013SZ0006, 2015SZ0230, 2018JY0089 and 2017HH0063)1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZY2016104)Youth Researcher Funding of Sichuan University (Grant No. 2017SCU11042 and 2017SCU04A17)Research Funding of Sichuan Health and Family Planning Commission (Grant No. 17PJ159,18PJ434 and 18PJ453).
文摘Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.
基金supported by the National Natural Science Foundation of China(No.8212010801,82371699 and 82401977)the National Key Research and Development Project(No.2022YFC2704602 and 2022YFC2704502)the Major Project of Shanghai Municipal Education Commission's Scientific Research and Innovation Plan(No.2021-01-07-00-07-E00144)。
基金Supported by National Natural Science Foundation of China,No.81872036Talent Innovation and Entrepreneurship Plan of Chengguan District of Lanzhou City,No.2019RCCX0038Science and Technology Plan of Chengguan District of Lanzhou City,No.2019JSXC0092.
文摘BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.
