title: Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha.
abstract: OBJECTIVE
  Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development, signaling and function. We investigated whether HDSMCs are capable of expressing and releasing MCP-1, IL-6 and SCF in response to IL-4, IL-13, IL-1beta and tumor necrosis factor-alpha.
  
  
  METHODS
  HDSMCs were isolated and cultured using an explant technique. Protein expression, and the secretion of MCP-1, IL-6 and SCF were assayed by semiquantitative reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Unstimulated cells released low amounts of MCP-1, IL-6 and SCF. In cells stimulated by IL-4 MCP-1 mRNA was up-regulated by a mean factor +/- SD of 3.5 +/- 1.3, IL-6 mRNA was up-regulated by 3.8 +/- 1.3, the soluble form of SCF was up-regulated by 3.2 +/- 0.6 and the membrane bound form of SCF was up-regulated by 7.9 +/- 5.6. For IL-13 stimulated cells the values were 2.6 +/- 1.5, 3.6 +/- 2.1, 2.9 +/- 1.6 and 5.7 +/- 3.7, respectively. Soluble SCF mRNA expression was 5 times higher than the expression of mSCF mRNA. IL-4 and IL-13 given separately stimulated MCP-1, IL-6 and SCF secretion in a concentration (0.01 to 100 ng/ml) and time (0 to 24 hours) dependent manner. Furthermore, IL-1beta and tumor necrosis factor-alpha alone induced significant release of MCP-1, IL-6 and SCF but in combination with IL-4 or IL-13 it induced greater secretion of MCP-1, IL-6 and SCF.
  
  
  CONCLUSIONS
  To our knowledge these findings demonstrate for the first time that HDSMCs express and release MCP-1 and IL-6, and show relatively high expression of soluble SCF. This supports our hypothesis that HDSMCs may have an active role by orchestrating the local inflammatory response in the bladder wall with possible implications for the pathophysiology of detrusor mastocytosis.
authors.affiliation: Smooth Muscle Laboratory, Herlev Hospital, University of Copenhagen, Denmark. Bouchelouche@mail.tele.dk
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bouchelouche
authors.forename: Lars
authors.initials: L
authors.lastname: Andresen
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.forename: Jorgen
authors.initials: J
authors.lastname: Nordling
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.forename: Pierre
authors.initials: P
authors.lastname: Bouchelouche
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D019089:Stem Cell Factor / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D007375:Interleukin-1; D018793:Interleukin-13; D015850:Interleukin-6; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4