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Interleukin-1β upregulates Na+-K+-2Cl− cotransporter in human middle ear epithelia

Other Titles
 Interleukin-1beta upregulates Na+-K+-2Cl- cotransporter in human middle ear epithelia 
 Su Jin Kim  ;  Jae Young Choi  ;  Joo-Heon Yoon  ;  Min Goo Lee  ;  Wan Namkung  ;  Eun Jin Son 
 JOURNAL OF CELLULAR BIOCHEMISTRY, Vol.101(3) : 576-586, 2007 
Journal Title
Issue Date
Ammonium Chloride/metabolism ; Cells, Cultured ; Ear, Middle/cytology ; Ear, Middle/drug effects* ; Ear, Middle/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/drug effects* ; Epithelial Cells/metabolism ; Humans ; Hydrogen-Ion Concentration ; Immunoblotting ; Immunohistochemistry ; Interleukin-1beta/pharmacology* ; Otitis Media with Effusion/metabolism ; Otitis Media with Effusion/pathology ; Sodium-Potassium-Chloride Symporters/metabolism* ; Time Factors
middle ear ; human ; Naþ-Kþ-2Cl cotransporter ; interleukin-1b ; otitis media with effusion
Disruption of periciliary fluid homeostasis is the main pathogenesis of otitis media with effusion (OME), one of the most common childhood diseases. Although the underlying molecular mechanisms are unclear, it has been suggested that the altered functions of ion channels and transporters are involved in the fluid collection of middle ear cavity of OME patients. In the present study, we analyzed the effects of a major cytokine interleukin (IL)-1β, which was known to be involved in the pathogenesis of OME, on Na+-K+-2Cl− cotransporter (NKCC) in human middle ear cells. Intracellular pH (pHi) was measured in primary cultures of normal human middle ear epithelial (NHMEE) cells using a double perfusion chamber, which enabled us to analyze the membrane-specific transporter activities. NKCC activities were estimated by the pHi reduction due to bumetanide-sensitive intracellular uptake of NHmath image. In NHMEE cells, NKCC activities were observed only in the basolateral membrane, and immunoblotting using specific antibodies revealed the expression of NKCC1. Interestingly, IL-1β treatments augmented the basolateral NKCC activities and increased NKCC1 expression. In addition, IL-1β treatments stimulated bumetanide-sensitive fluid transport across the NHMEE cell monolayers. Furthermore, an elevated NKCC1 expression was observed in middle ear cells from OME patients when compared to those from control individuals. The above results provide in vitro and in vivo evidence that the inflammatory cytokine IL-1β upregulates NKCC1 in middle ear epithelial cells, which would be one of the important underlying mechanisms of excess fluid collection in OME patients.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Son, Eun Jin(손은진)
Yoon, Joo Heon(윤주헌)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
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