Jugde F, Alizadeh M, Boissier C, Chantry D, Siproudhis L, Corbinais S, Quelvennec E, Dyard F, Campion J P, Gosselin M, Bretagne J F, Sémana G, Heresbach D
Immunology Laboratory, Gurifa EA 1257, Rennes University, France.
Eur Cytokine Netw. 2001 Jul-Sep;12(3):468-77.
Chemokines and their receptors are involved in the migration of different mononuclear cells. Among them macrophages-derived chemokines (MDC) and thymus-and activation regulated chemokine (TARC) belong to a new cluster of genes involve in Th2 lymphocytes homing. Cytokines appear to play a significant role in pathogenesis of inflammatory bowel diseases with an excessive Th1 response in chronic lesions of Crohn's disease (CD) and a Th2 pattern in both earlier mucosal CD lesions and in mucosa of ulcerative colitis (UC). Here we demonstrate that RNAm coding for MDC and TARC are expressed in mucosa from CD and UC patients. Using real-time fluorescent RT-PCR, MDC and TARC mRNA were increased in CD inflamed mucosa. Moreover MDC and TARC transcripts were increased in inflamed CD specimen compared to non-involved CD mucosa. These differences both discriminate CD from UC patients. Additionally, MDC protein was produced in isolated mononuclear cells from peripheral blood (PBMC) or mucosa (LPMC) from UC and CD patients: spontaneously, MDC production from PBMC was increased in CD compared to UC patients. MDC production from CD PBMC was also higher than that found in healthy controls. Together, these data indicate that MDC should be involved in the lymphocytes homing in mucosa from CD patients.
趋化因子及其受体参与不同单核细胞的迁移。其中,巨噬细胞衍生趋化因子(MDC)和胸腺与活化调节趋化因子(TARC)属于参与Th2淋巴细胞归巢的一组新基因。细胞因子在炎症性肠病的发病机制中似乎起着重要作用,在克罗恩病(CD)的慢性病变中存在过度的Th1反应,而在早期黏膜CD病变和溃疡性结肠炎(UC)的黏膜中则呈现Th2模式。在此我们证明,编码MDC和TARC的RNA在CD和UC患者的黏膜中表达。使用实时荧光逆转录聚合酶链反应(RT-PCR),发现MDC和TARC mRNA在CD炎症黏膜中增加。此外,与未受累的CD黏膜相比,炎症性CD标本中的MDC和TARC转录本增加。这些差异均有助于区分CD患者与UC患者。另外,UC和CD患者外周血(PBMC)或黏膜(LPMC)中分离出的单核细胞可产生MDC蛋白:自发性地,与UC患者相比,CD患者PBMC产生的MDC增加。CD患者PBMC产生的MDC也高于健康对照者。总之,这些数据表明MDC应参与CD患者黏膜中的淋巴细胞归巢。