Cyclic Stretch Augments Production of Neutrophil Chemokines and Matrix Metalloproteinase-1 in Human Uterine Smooth Muscle Cells



Kaori Koga, Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo Bunkyo Tokyo, 113-8655, Japan. E-mail:



The aim of this study was to investigate the impact of uterine contraction on the immune environment within the uterus during parturition.

Method of study

Uterine smooth muscle cells (USMC) were isolated from uterine myometrial tissues and cultured. The effects of cyclic stretch on mRNA and/or protein expression of IL-8, Groα, and pro-MMP-1 by USMC were measured using RT-PCR and ELISA. Neutrophil chemotactic activity in conditioned media was evaluated using migration assays. To evaluate the effect of progesterone (P4), USMC were pretreated with P4 for 24 hr.


Cyclic stretch increased IL-8 and Groα mRNA and protein and pro-MMP-1 production significantly. Supernatants from stretched cells induced neutrophil chemotactic activity significantly; these effects were abrogated by anti-IL-8 or Groα neutralizing antibodies. Stretch effects were reduced by P4.


These results suggest that uterine contraction may induce neutrophil infiltration and MMP-1 production, which may contribute to cervical ripening and rupture of membrane. The inhibitory effects of P4 may explain the mechanism by which progestin prevents preterm labor.