唐 莼, 李 昀, 林小軍, 葉靜華, 李偉念, 何志翔, 李芳菲, 蔡小燕△
(1廣州市第一人民醫(yī)院風(fēng)濕免疫科,廣東 廣州 510180; 2中山大學(xué)附屬第三醫(yī)院心胸外科,廣東 廣州 510630)
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泌乳素促進(jìn)類風(fēng)濕關(guān)節(jié)炎患者外周血單個(gè)核細(xì)胞分泌白細(xì)胞介素-6*
唐 莼1, 李 昀2, 林小軍1, 葉靜華1, 李偉念1, 何志翔1, 李芳菲1, 蔡小燕1△
(1廣州市第一人民醫(yī)院風(fēng)濕免疫科,廣東 廣州 510180;2中山大學(xué)附屬第三醫(yī)院心胸外科,廣東 廣州 510630)
目的: 探討類風(fēng)濕關(guān)節(jié)炎(RA)患者血清泌乳素(PRL)水平與疾病活動(dòng)程度的關(guān)系,以及PRL促進(jìn)外周血單個(gè)核細(xì)胞(PBMCs)分泌白細(xì)胞介素-6(IL-6)的機(jī)制。方法:收集我院2015年3月至9月40例初治RA患者臨床及實(shí)驗(yàn)室資料。采用化學(xué)發(fā)光免疫分析法(CLIA)檢測(cè)血清PRL水平,ELISA檢測(cè)IL-6水平,RT-qPCR 檢測(cè)泌乳素受體(PRLR) mRNA的表達(dá),Western blot法檢測(cè)MAPK通路相關(guān)蛋白p-p38的蛋白水平。結(jié)果:RA患者血清PRL水平明顯升高(P<0.01),活動(dòng)期RA患者PRL水平明顯高于非活動(dòng)期RA患者(P<0.01)。PRL水平與DAS28評(píng)分、ESR和CRP呈正相關(guān)(P<0.01)。RA患者PBMCs中PRLR水平明顯升高(P<0.01)。PRL可誘導(dǎo)PBMCs分泌IL-6,siRNA沉默PRLR或采用MAPK通路抑制劑可抑制IL-6的產(chǎn)生。結(jié)論:RA患者血清PRL升高與DAS28評(píng)分、ESR和CRP呈正相關(guān),PRL可作為預(yù)測(cè)RA嚴(yán)重程度的指標(biāo)。PRL通過與PRLR相互作用,激活p38 MAPK通路,從而促進(jìn)IL-6分泌。
類風(fēng)濕關(guān)節(jié)炎; 泌乳素; 白細(xì)胞介素-6; p38
類風(fēng)濕性關(guān)節(jié)炎(rheumatoid arthritis,RA)是一種慢性、彌漫性的自身免疫性疾病,其主要侵犯外周關(guān)節(jié)引起滑膜炎癥,進(jìn)而導(dǎo)致不可逆的關(guān)節(jié)破壞,同時(shí)關(guān)節(jié)外的多處器官包括心、肺、雙眼及皮膚均可受累[1]。目前認(rèn)為RA以關(guān)節(jié)炎癥、滑膜增生和血管翳形成為主要特征,但迄今為止,其發(fā)病機(jī)制仍未完全闡明。研究表明,類風(fēng)濕關(guān)節(jié)炎的疾病進(jìn)展與異常的免疫系統(tǒng)釋放前炎癥細(xì)胞因子密切相關(guān),從而導(dǎo)致持續(xù)性滑膜炎癥和關(guān)節(jié)軟骨或骨的破壞。其中白細(xì)胞介素-6(interleukin-6,IL-6)是一種多效性前炎癥細(xì)胞因子,也是RA患者血清和滑液中含量最豐富的細(xì)胞因子。IL-6是RA的致病源頭因素之一,IL-6參與RA致病過程中早期B和T細(xì)胞的活化,并參與全程致病過程[2]。泌乳素(prolactin,PRL)主要由垂體前葉產(chǎn)生,在細(xì)胞免疫和體液免疫過程發(fā)揮重要作用[3]。絲裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)通路是調(diào)節(jié)細(xì)胞生長(zhǎng)、分化、對(duì)環(huán)境應(yīng)激適應(yīng)、炎癥反應(yīng)等多種病理生理過程的途徑。RA患者中PRL是否通過MAPK通路促進(jìn)IL-6釋放尚無文獻(xiàn)報(bào)告。本研究通過檢測(cè)RA患者PRL、PRLR、IL-6水平及MAPK通路 p-p38蛋白的表達(dá),探討PRL通過MAPK通路促進(jìn)PBMCs分泌IL-6的作用機(jī)制。
1 研究對(duì)象
收集2015年3~9月廣州市第一人民醫(yī)院風(fēng)濕科收治的40例初治RA患者臨床資料,所有患者均符合2009年美國(guó)風(fēng)濕病協(xié)會(huì)的RA 分類診斷標(biāo)準(zhǔn)[4]。排除常見引起繼發(fā)性高泌乳素血癥的原因,如泌乳素瘤、下丘腦或垂體病變、甲狀腺功能減退、慢性腎功能不全、嚴(yán)重肝病、藥物(口服避孕藥、雌激素、抗精神病藥、抗抑郁藥、西米替丁等)、妊娠及哺乳等。其中男9例,女31例,年齡(30.5±16.3)歲(16~61歲)。根據(jù) RA疾病活動(dòng)度積分(disease activity score 28,DAS28)進(jìn)行活動(dòng)評(píng)分,DAS28≥2.6為活動(dòng)期,DAS28<2.6為穩(wěn)定期。RA活動(dòng)患者26例,穩(wěn)定患者14例。同時(shí)采用20例健康體檢成人標(biāo)本為對(duì)照組。
2 主要試劑
抗泌乳素受體(prolactin receptor, PRLR)抗體、p38抗體、p-p38抗體和PRLRsiRNA購(gòu)自Santa Cruz;泌乳素化學(xué)發(fā)光免疫分析(chemiluminescence immunoassay,CLIA)試劑盒購(gòu)自Siemens Healthcare Diagnostics;IL-6 ELISA檢測(cè)試劑盒和泌乳素蛋白檢測(cè)試劑盒購(gòu)自R&D Systems;轉(zhuǎn)染、RT-qPCR和Western blot實(shí)驗(yàn)所需試劑均購(gòu)自Invitrogen;DNA純化盒購(gòu)自Promega;淋巴細(xì)胞分離液購(gòu)自Nycomed;MAPK抑制劑PD98059購(gòu)自Sigma-Aldrich。
3 主要方法
3.1 外周血單個(gè)核細(xì)胞(peripheral blood mononuclear cells, PBMCs)分離 用10 mL肝素抗凝管采集患者及對(duì)照者肘靜脈血5 mL,根據(jù)淋巴細(xì)胞分離的要求進(jìn)行密度梯度離心,獲得的PBMCs用RPMI-1640培養(yǎng)以進(jìn)行進(jìn)一步實(shí)驗(yàn)。
3.2 實(shí)時(shí)熒光定量PCR(RT-qPCR)實(shí)驗(yàn) TRIzol法提取PBMCs總RNA并定量。按試劑盒說明進(jìn)行逆轉(zhuǎn)錄合成cDNA。采用MiniOpticon PCR儀(Bio-Rad)進(jìn)行RT-qPCR檢測(cè),GAPDH作為內(nèi)參照。PRLR的上游引物為5’-GCAAGCAGTACACCTCCATG-3’,下游引物為 5’-GAGCGTGAACCAACCAGTTT-3’;IL-6的上游引物為5’-CAAATTCGGTACATCCTC-3’,下游引物為 5’-CTGGCTTGTTCCTCACTA-3’;GAPDH的上游引物為5’-ACCACAGTCCATGCCATCAC-3’,下游引物 為5’-TCCACCACCCTGTTGCTGTA-3’。反應(yīng)體系為20 μL,反應(yīng)條件為95 ℃ 3 min;95 ℃ 10 s,55 ℃ 30 s,39個(gè)循環(huán);在每個(gè)循環(huán)延伸末端點(diǎn)收集熒光信號(hào),繪制擴(kuò)增曲線。基因的表達(dá)量用2-ΔΔCt表示。
3.3 Western blot實(shí)驗(yàn) 預(yù)冷PBS洗滌細(xì)胞3次,加入全蛋白裂解液后冰上裂解10 min收集蛋白。將抽提蛋白用BCA法定量后,取50 μg上樣,于100 V進(jìn)行SDS-PAGE;電泳,結(jié)束后以90 V、90 min將蛋白轉(zhuǎn)移至PVDF膜; 5% TBS牛奶室溫封閉30 min, I 抗(0.5~1 mg/L)室溫孵育1 h,HRP結(jié)合的 II 抗室溫孵育1 h。每次抗體孵育后用TBST洗膜15 min 3次。ECL試劑盒進(jìn)行發(fā)光反應(yīng),壓片、顯影、定影,觀察蛋白條帶并進(jìn)行ImageJ圖像分析。
3.4 酶聯(lián)免疫吸附實(shí)驗(yàn)(ELISA) 將PBMCs細(xì)胞1 500 r/min水平離心10 min,取上清按IL-6 ELISA檢測(cè)試劑盒的要求檢測(cè)IL-6水平。
3.5 化學(xué)發(fā)光免疫分析 血清PRL檢測(cè)采用CLIA法,根據(jù)Siemens PRL試劑盒要求檢測(cè)。根據(jù)試劑盒要求,定義PRL濃度>17.7 μg/L(男性)或29.2 μg/L(女性)為高泌乳素血癥。
3.6 PRL刺激PBMCs 將分離得到的RA患者及健康成人的PBMCs和培養(yǎng)液鋪于6孔板內(nèi),使得每孔細(xì)胞數(shù)量為1×109/L,然后加入濃度為200 μg/L的PRL。處理后的細(xì)胞放入37 ℃、5% CO2的培養(yǎng)箱內(nèi)培養(yǎng)48 h,再采用ELISA法檢測(cè)IL-6水平。
3.7 細(xì)胞轉(zhuǎn)染 選擇對(duì)數(shù)生長(zhǎng)期的PBMCs進(jìn)行轉(zhuǎn)染,轉(zhuǎn)染前1 d將生長(zhǎng)良好的細(xì)胞接種到6孔板中,每孔中接種約5×104個(gè)細(xì)胞,加入0.5 mL含10% PBS的RPMI-1640培養(yǎng)液,在37 ℃、5% CO2培養(yǎng)箱中培養(yǎng)24 h,當(dāng)細(xì)胞密度達(dá)到50%~80%時(shí),根據(jù)Invitrogen 公司的轉(zhuǎn)染試劑說明書,將PRLRsiRNA轉(zhuǎn)染至PBMCs以沉默PRLR。然后在37 ℃、5% CO2條件下培養(yǎng)4~6 h,更換正常培養(yǎng)液以終止轉(zhuǎn)染。轉(zhuǎn)染后,于24 h內(nèi)收集細(xì)胞,檢測(cè)瞬時(shí)表達(dá)情況及IL-6水平。
3.8 RA相關(guān)血液學(xué)指標(biāo)的檢測(cè) 采集患者及對(duì)照組血液,由我院檢驗(yàn)科按照要求檢測(cè)RA相關(guān)血液學(xué)指標(biāo),包括:(1) 血沉(erythrocytes edimentation rate,ESR)采用魏氏法,其正常值分別為男性≤15 mm/h,女性≤20 mm/h; (2) C反應(yīng)蛋白(C-reactive protein, CRP)采用散射比濁法,其正常值為<6 mg/L;(3) 類風(fēng)濕因子(rheumatoid factor,RF)采用散射比濁法,其正常值為≤15 IU/mL。
4 統(tǒng)計(jì)學(xué)處理
應(yīng)用統(tǒng)計(jì)學(xué)軟件SPSS 19.0進(jìn)行統(tǒng)計(jì)學(xué)處理。計(jì)量數(shù)據(jù)用均數(shù)±標(biāo)準(zhǔn)差(mean±SD)表示,兩組比較采用t檢驗(yàn),多組比較用單因素方差分析檢驗(yàn)。計(jì)數(shù)資料組間比較采用2檢驗(yàn)。PRL與臨床參數(shù)的相關(guān)性分析運(yùn)用Pearson相關(guān)分析方法。以P<0.05為差異有統(tǒng)計(jì)學(xué)顯著性。
1 RA患者血清PRL水平明顯升高
RA患者PRL水平明顯高于健康組(P<0.01);而活動(dòng)期RA患者PRL水平明顯高于非活動(dòng)期RA患者(P<0.01),見圖1。根據(jù)血清PRL水平,將RA患者分為高PRL組和正常組,結(jié)果提示,高PRL組的活動(dòng)期RA患者明顯多于非活動(dòng)期RA患者(P<0.01),見表1。
Figure 1.PRL was increased in the RA patients. A: serum PRL levels of RA patients and healthy controls were detected by CLIA; B: serum PRL levels of active or inactive RA patients were detected by CLIA. Mean±SD.**P<0.01vscontrol;##P<0.01vsinactive RA.
圖1 RA患者血清PRL明顯升高
表1 血清PRL水平與RA患者疾病活動(dòng)的相關(guān)性
Table 1. The correlation between serum PRL and disease activity of RA patients
GroupRAActive(n=26)Inactive(n=14)2PNormalPRL(n=19)71212.2980.001HighPRL(n=21)192
2 RA患者血清PRL與臨床參數(shù)的關(guān)系
RA患者血清PRL水平與DAS28評(píng)分呈正相關(guān)(P<0.01)。同時(shí),PRL水平與ESR和CRP呈正相關(guān)(P<0.01),而與RF水平無明顯相關(guān)性,見圖2。
3 RA患者PBMCs中PRLR高表達(dá)
RT-qPCR檢測(cè)PBMCs中PRLR的表達(dá),結(jié)果發(fā)現(xiàn)RA患者PBMCs的PRLR水平明顯高于對(duì)照組(P<0.01),見圖3。
Figure 2.The correlations between serum PRL and clinical parameters of the RA patients. PRL levels were positively correlated with DAS28 score (A), ESR level (B) and CRP level (C) of the RA patients.
圖2 RA患者血清PRL與臨床參數(shù)的關(guān)系
Figure 3. The mRNA expression of PRLR in the PBMCs of the RA patients was enhanced (detected by RT-qPCR).**P<0.01vscontrol.
圖3 RA患者PBMCs的PRLR mRNA表達(dá)增高
4 PRL誘導(dǎo)PBMCs分泌IL-6
PRL誘導(dǎo)的RA患者PBMCs分泌IL-6的水平明顯升高(P<0.01)。用siRNA沉默PRLR后,IL-6的表達(dá)水平明顯下調(diào)(P<0.01),見圖4。
5 PRL通過MAPK通路誘導(dǎo)PBMCs分泌IL-6
采用MAPK抑制劑PD98059作用于PBMCs后,PRL誘導(dǎo)的分泌IL-6水平明顯下降(P<0.01)。Western blot法檢測(cè)p-p38的蛋白水平,結(jié)果發(fā)現(xiàn)PRL可誘導(dǎo)PBMCs上調(diào)p-p38的水平,而用siRNA沉默PRLR后,p-p38的蛋白水平明顯下降,見圖5。
IL-6是具有多種生物活性的多效性促炎癥細(xì)胞因子,近年來的研究表明,IL-6/可溶性IL-6受體(soluble interleukin-6 receptor,sIL-6R)與RA的發(fā)病機(jī)制和疾病進(jìn)展密切相關(guān)。IL-6/sIL-6R可以打破Thl7/Treg的平衡[5],促進(jìn)B細(xì)胞發(fā)生、分化,并產(chǎn)生大量自身抗體[6]。類風(fēng)濕關(guān)節(jié)炎患者血清及關(guān)節(jié)滑液中IL-6/sIL-6R的濃度較高,其水平與受累關(guān)節(jié)數(shù)量、疾病活動(dòng)、晨僵持續(xù)時(shí)間、X線改變等密切相關(guān)。目前,抗sIL-6R的人源化抗體Tocilizumab已上市,并在RA的治療中取得顯著療效。PRL主要由垂體前葉產(chǎn)生,影響乳腺的生長(zhǎng)和分化,促進(jìn)乳汁分泌。研究表明,PRL參與細(xì)胞免疫和體液免疫過程[3, 7],影響人類免疫細(xì)胞的增殖和分化[8],近期研究表明, PRL與RA的發(fā)病機(jī)制相關(guān),RA患者血清及滑膜液中的PRL 水平明顯升高,其水平與類風(fēng)濕關(guān)節(jié)炎疾病活動(dòng)度及影像學(xué)Larsen 評(píng)分相關(guān)[9]。
Figure 4.IL-6 release from the PBMCs was induced by PRL. A: PBMCs were stimulated by PRL. The IL-6 release was tested by ELISA. Mean±SD.n=12.**P<0.01vsvehicle. B:PRLRwas knockdown by transfection withPRLRsiRNA (si-PRLR) in the PBMCs of RA patients. The knockdown effect was certificated by Western blot. Mean±SD.n=6.**P<0.01vscontrol. C: the IL-6 release was detected by ELISA. Mean±SD.n=12.*P<0.05,**P<0.01vsPRL+si-PRLR;##P<0.01vssi-PRLR.
圖4 PRL誘導(dǎo)RA 病人的PBMCs分泌IL-6
Figure 5.IL-6 release induced by PRL was interrupted by MAPK inhibitor. A: the IL-6 release was detected by ELISA. Mean±SD.n=12.*P<0.05,**P<0.01vsPRL+PD98059;##P<0.01vsPD98059. B: the protein level of phosphorylated p38 was detected by Western blot. Mean±SD.n=12.*P<0.05,**P<0.01vsPRL+si-PRLR;##P<0.01vssi-PRLR.
圖5 MAPK抑制劑可阻斷PRL誘導(dǎo)PBMCs分泌IL-6
本研究發(fā)現(xiàn),RA患者PBMCs中PRLR表達(dá)水平明顯高于對(duì)照組,提示PBMCs中PRL可能與PRLR相互作用而產(chǎn)生病理效應(yīng)。大量證據(jù)表明,PRL/PRLR在糖代謝、脂代謝及細(xì)胞、體液免疫調(diào)節(jié)及腫瘤發(fā)生發(fā)展中具有重要作用[10],可促進(jìn)細(xì)胞增殖、分化及細(xì)胞因子的產(chǎn)生[11]。本研究發(fā)現(xiàn)RA患者PBMCs經(jīng)過PRL處理后,分泌IL-6明顯升高,而siRNA沉默PRLR后,PRL誘導(dǎo)的IL-6分泌作用明顯受到抑制,提示PRL/PRLR相互作用在PBMCs分泌IL-6的機(jī)制中具有關(guān)鍵作用。
MAPK是一組能被不同的細(xì)胞外刺激,如細(xì)胞因子、神經(jīng)遞質(zhì)、激素、細(xì)胞應(yīng)激及細(xì)胞黏附等激活的絲氨酸-蘇氨酸蛋白激酶,MAPK通路調(diào)節(jié)細(xì)胞生長(zhǎng)、分化、對(duì)環(huán)境的應(yīng)激適應(yīng)、炎癥反應(yīng)等多種重要的細(xì)胞病理生理過程[12]。RA患者中PRL是否通過MAPK通路促進(jìn)IL-6釋放目前暫無相關(guān)文獻(xiàn)報(bào)告。本研究發(fā)現(xiàn),PRL可誘導(dǎo)MAPK通路蛋白p-p38表達(dá)明顯升高,而siRNA沉默PRLR后,p-p38表達(dá)水平明顯下降,同時(shí)IL-6分泌明顯減少。以上結(jié)果提示RA患者PBMCs中PRL通過與PRLR相互作用激活MAPK通路,從而促進(jìn)IL-6分泌。
綜上所述,RA患者血清PRL水平明顯升高,且與DAS28評(píng)分、ESR和CRP呈正相關(guān),提示PRL可作為預(yù)測(cè)RA嚴(yán)重程度的指標(biāo)。PBMCs表達(dá)高水平PRLR,PRL通過激活MAPK通路促進(jìn)IL-6分泌,提示PRL/PRLR-MAPK p38-IL-6通路在RA發(fā)病中具有一定作用,對(duì)其進(jìn)一步研究將有利于對(duì)RA發(fā)病機(jī)制的深入理解。
[1] Kaur S, White S, Bartold PM. Periodontal disease and rheumatoid arthritis: a systematic review[J]. J Dent Res, 2013, 92(5):399-408.
[2] Liu Y, Mu R, Wang S, et al. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis[J]. Arthritis Res Ther, 2010, 12(6): R210.
[3] Zen M, Ghirardello A, Iaccarino L, et al. Hormones, immune response, and pregnancy in healthy women and SLE patients[J]. Swiss Med Wkly, 2010,140 (13-14):187-201.
[4] Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative [J]. Arthritis Rheum, 2010, 62(9):2569-2581.
[5] Kimura A, Kishimoto T. IL-6: regulator of Treg/Thl7 ba-lance [J]. Eur J Immunol, 2010, 40(7):1830-1835.
[6] Dienz O, Eaton SM, Bond JP, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+T cells[J]. J Exp Med, 2009, 206(1): 69-78.
[7] 戴 冽,吳毅梅,鄭東輝,等. 血清泌乳素與系統(tǒng)性紅斑狼瘡患者腎損害的相關(guān)性[J]. 中國(guó)病理生理雜志, 2007, 23(7):1437-1438, 1441.
[8] Tomio A, Schust DJ, Kawana K, et al. Prolactin can modulate CD4+T-cell response through receptor-mediated alterations in the expression of T-bet[J]. Immunol Cell Biol, 2008, 86 (7):616-621.
[9] Fojtíková M, Tomasová Studnková J, Filková M, et al. Elevated prolactin levels in patients with rheumatoid arthritis: association with disease activity and structural damage [J]. Clin Exp Rheumatol, 2010, 28(6):849-854.
[10]Lopez-Pulido EI, Muoz-Valle JF, Del Toro-Arreola S, et al. High expression of prolactin receptor is associated with cell survival in cervical cancer cells[J]. Cancer Cell Int, 2013, 13(1):103.
[11]Sodhi A, Tripathi A. Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophagesinvitro: involvement of p-38 MAP kinase, STAT3 and NF-κB[J]. Cytokine, 2008, 41(2):162-173.
[12]Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases[J]. Science, 2002, 298(5600):1911-1912.
(責(zé)任編輯: 林白霜, 羅 森)
Prolactin induces interleukin-6 expression in PBMCs of rheumatoid arthritis patients
TANG Chun1, LI Yun2, LIN Xiao-jun1, YE Jing-hua1, LI Wei-nian1, HE Zhi-xiang1, LI Fang-fei1, CAI Xiao-yan1
(1DepartmentofRheumatology,GuangzhouFirstPeople’sHospital,Guangzhou510180,China;2DepartmentofCardiothoracicSurgery,TheThirdAffiliatedHospitalofSunYat-senUniversity,Guangzhou510630,China.E-mail:xycai@medmail.com.cn)
AIM: To investigate the correlation between serum prolactin (PRL) levels and disease activity in rheumatoid arthritis (RA) patients, and the regulatory role of PRL in interleukin-6 (IL-6) release from peripheral blood mononuclear cells (PBMCs), and to explore the MAPK-related mechanism of IL-6 release in PBMCs. METHODS: The clinicopathologic and hematologic parameters of 40 new-onset RA patients in the Department of Rheumatology of our hospital between March and September 2015 were collected. Chemilumineseent immunoassay (CLIA) was used to detect the serum PRL levels in the 40 RA patients and 20 healthy controls. The levels of IL-6 secretion by the PBMCs were evaluated using ELISA. Quantitative real-time PCR was employed to examine the mRNA expression of prolactin receptor (PRLR). MAPK pathway protein p-p38 levels were evaluated by Western blot. RESULTS: Serum PRL level in the RA patients was significantly higher than that in the healthy controls (P<0.01). Serum PRL level in active RA patients was significantly higher than that in inactive RA patients (P<0.01). Serum PRL level was positively correlated with DAS28, ESR and CRP (P<0.01). The expression of PRLR in the PBMCs was markedly increased in the RA patients than that in the healthy samples (P<0.01). Exposure of the PBMCs to PRL in the culture increased the release of IL-6, which was abolished byPRLRgene silencing or blocking the MAPK pathway. CONCLUSION: Serum PRL level is related to DAS28, ESR and CRP of RA patients and could be used as a predictor of disease activity. PRL/PRLR-p38 MAPK-IL-6 pathway may play a central role in the pathogenesis of RA.
Rheumatoid arthritis; Prolactin; Interleukin-6; p38
1000- 4718(2016)11- 2062- 05
2016- 05- 19
2016- 09- 18
廣東省科技計(jì)劃項(xiàng)目(No.2012B031800274)
R363; R593.2
A
10.3969/j.issn.1000- 4718.2016.11.024
雜志網(wǎng)址: http://www.cjpp.net
△ 通訊作者 Tel: 020-81048664; E-mail: xycai@medmail.com.cn