title: Stretch and inflammatory cytokines drive myometrial chemokine expression via NF-κB activation.
abstract: Both human preterm labor (PTL) and term labor are consistently associated with a chemokine-induced inflammatory infiltration of the myometrium. However, what regulates myometrial chemokine expression and whether the increase in expression precedes the onset of labor, and so may have a role in its causation, or occurs after, and is simply a consequence of labor, is uncertain. Therefore, we assessed 1) chemokine expression in nonlaboring and laboring myometrial samples obtained at and before term and 2) the factors that regulate myometrial chemokine expression. We found that term labor was characterized by an increase in CXCL8 and CCL2 in both upper and lower segments, whereas PTL was associated with a distinct pattern of chemokine expression, with increases in CCL5, CXCL5, and CCL20 in the lower segment myometrium only. Further, we found that chemokine expression in myometrial cell cultures was increased by stretch and inflammatory cytokines and reduced by prostglandins and oxytocin and that the primary mediator of stretch and cytokine effects was nuclear factor κB (NF-κB) and to a lesser extent MAPK. These data show that PTL appears to be associated with a distinct pattern of chemokine expression, that stretch and cytokines both drive myometrial chemokine expression primarily via activation of NF-κB. These data suggest that the modulation of NF-κB activity may be of potential benefit in the management of PTL.
authors: Imperial College Parturition Research Group, Academic Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom.
authors: Renyi
authors: R
authors: Hua
authors: James E
authors: JE
authors: Pease
authors: Suren R
authors: SR
authors: Sooranna
authors: Jonathan M
authors: JM
authors: Viney
authors: Scott M
authors: SM
authors: Nelson
authors: Les
authors: L
authors: Myatt
authors: Philip R
authors: PR
authors: Bennett
authors: Mark R
authors: MR
authors: Johnson
mesh_terms: D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007743:Labor, Obstetric / Q000235:genetics / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: C111835:CCL2 protein, human; C108355:CCL20 protein, human; C483024:CCL5 protein, human; C486263:CXCL5 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D018946:Chemokine CCL5; D054365:Chemokine CXCL5; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger