Interleukin-33/ST2 signaling promotes production of interleukin-6 and interleukin-8 in systemic inflammation in cigarette smoke-induced chronic obstructive pulmonary disease mice

Biochem Biophys Res Commun. 2014 Jul 18;450(1):110-6. doi: 10.1016/j.bbrc.2014.05.073. Epub 2014 May 24.

Abstract

Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice.

Keywords: Chronic obstructive pulmonary disease; Interleukin-33; Mouse models; Peripheral blood mononuclear cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-6 / immunology*
  • Interleukin-8 / immunology*
  • Interleukins / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Receptors, Interleukin / immunology*
  • Systemic Inflammatory Response Syndrome / etiology
  • Systemic Inflammatory Response Syndrome / immunology*
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-6
  • Interleukin-8
  • Interleukins
  • Receptors, Interleukin
  • Tobacco Smoke Pollution