Cysteinyl leukotriene upregulates IL-11 expression in allergic airway disease of mice.
BACKGROUND
Chronic airway inflammation and airway remodeling are important features of bronchial asthma. IL-11 is one of the important mediators involved in the process of airway inflammation and remodeling. Cysteinyl leukotrienes (cysLTs) play roles in recruitment of inflammatory cells, airway smooth muscle contraction, vascular leakage, increased mucus secretion, decreased mucociliary clearance, and airway fibrosis.


OBJECTIVE
An aim of the present study was to determine the effect of the cysLTs on the regulation of IL-11 expression.


METHODS
We used a C57BL/6 mouse model of allergic airway disease and murine tracheal epithelial cells to examine the effects of cysLTs on the regulation of IL-11 expression.


RESULTS
Our present study with an ovalbumin-induced murine model of allergic airway disease revealed that levels of leukotriene C(4) (LTC(4)) in bronchoalveolar lavage fluids were increased and that administration of montelukast or pranlukast reduced the increased levels of LTC(4); the increased expression of IL-11 protein and mRNA in lung tissues; airway inflammation, bronchial hyperresponsiveness; the increased levels of TGF-beta(1), IL-4, and IL-13 in bronchoalveolar lavage fluids and lung tissues; and airway fibrosis. In addition, LTC(4) stimulates epithelial cells to produce IL-11. Our results also showed that cysLT type 1 receptor antagonists downregulated the activity of a transcription factor, nuclear factor kappaB, and BAY 11-7085 substantially reduced the increased levels of IL-11 after ovalbumin inhalation.


CONCLUSIONS
These results suggest that cysLTs regulate the IL-11 expression in allergic airway disease.


CONCLUSIONS
These findings provide one of the molecular mechanisms for the effects of cysLTs on airway inflammation and fibrosis in allergic airway diseases.
Lee
Kyung Sun
KS
Department of Internal Medicine, Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju, South Korea.
Kim
So Ri
SR
Park
Hee Sun
HS
Park
Seoung Ju
SJ
Min
Kyung Hoon
KH
Lee
Ka Young
KY
Jin
Sun Mi
SM
Lee
Yong Chul
YC
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D003521:Cyclopropanes; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D017370:Interleukin-11 / Q000096:biosynthesis* / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology; D010047:Ovalbumin; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013440:Sulfides; D013450:Sulfones / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000096:biosynthesis
D000085:Acetates; C416282:BAY 11-7085; D002867:Chromones; D003521:Cyclopropanes; D017370:Interleukin-11; D018793:Interleukin-13; D020024:Leukotriene Antagonists; D009570:Nitriles; D011804:Quinolines; D012333:RNA, Messenger; D013440:Sulfides; D013450:Sulfones; D051996:Transcription Factor RelA; D015847:Interleukin-4; D017997:Leukotriene C4; D017998:Leukotriene D4; D010047:Ovalbumin; D003094:Collagen; C093875:montelukast; C047681:pranlukast