Effects of Cytokines on Mechanical and Epithelial Bioelectric Responses to Methacholine and Hyperosmolarity in Guinea-Pig Airways: An In Vitro Study

Details

• Personal Author:
  Fedan, Jeffery S. ; Ismailoglu UB ; VanScott MR
• Description:
  We observed previously that lipopolysaccharide (LPS) 18 h after i.p. injection of guinea pigs increased transepithelial potential difference (V-t, hyperpolarization responses to methacholine, and hyperosmolarity-induced, epithelium-derived relaxing factor (EpDRF)-mediated relaxation responses, in excised and perfused tracheal segments. To investigate their roles in these changes, the effects of cytokines on in vitro epithelial bioelectric and smooth muscle mechanical responses were investigated using the isolated, perfused trachea preparation. Tracheas were incubated (6 h) with LPS or IL-beta, IL-13, IFN-gamma, TNF-alpha, singly or in combination. Incubation with LPS and cytomix (IL-1 beta, IL-4, IL-13, IFN-gamma, TNF-alpha together) had no effect oil muscle reactivity to methacholine, but potentiated D-mannitol-induced relaxation. Individually, IL-1 beta and IFN-gamma inhibited methacholine-induced contractions and potentiated D-mannitol-induced relaxation responses. TNF-alpha increased contractions to methacholine but had no effect on relaxation responses to D-mannitol. Methacholine elicited hyperpolarization in low concentrations and depolarization in high concentrations. The individual cytokines decreased the hyperpolarization response to low methacholine concentrations and increased the depolarization response to high methacholine concentrations but had no effect oil V-t responses to D-mannitol. Cytomix did not affect V-t responses to methacholine, but potentiated both the hyperpolarization and depolarization responses to D-mannitol. In Ussing chambers all agents except IL-i beta and IFN-gamma increased V-t decreased slightly but none of the other agents affected transepithelial resistance (R,). The results indicate that cytokines and LPS alter smooth muscle reactivity to methacholine, potentiate EpDRF-mediated relaxation responses and. thereby, mimic the effects of LPS treatment in vivo, but do not recapitulate LPS' effects on V-t responses. [Description provided by NIOSH]
• Subjects:
  Biochemistry Hypersensitivity Laboratories Lipids Musculoskeletal System Occupational Health Respiratory System Safety
• Keywords:
  Airway-obstruction Author Keywords: Epithelium-derived Relaxing Factor Biochemical-analysis Biodynamics Biological-effects Biological-function Cell-biology Cell-function Cell-metabolism Cellular-function Cellular-reactions Chemical-hypersensitivity Cytokine Guinea-pig Trachea Hyperosmolarity Inhalation-studies Laboratory-animals Laboratory-testing Lipopolysaccharide Muscle-function Muscle-physiology Muscle-relaxants Muscles Reaction-rates Smooth Muscle Contractility Transepithelial Potential Difference

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• ISSN:
  0014-2999
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  115-121
• Volume:
  612
• Issue:
  1
• NIOSHTIC Number:
  nn:20035581
• Citation:
  Eur J Pharmacol 2009 Jun; 612(1-3):115-121
• Contact Point Address:
  Jeffrey S. Fedan, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505
• Email:
  jsf2@cdc.gov
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  European Journal of Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:233eff32bf50fea7a890696dfd080f2cd562526e19e4479d363d392717af969f778bc28442d3d56ca57817e46262b74b6655da0c67597905cf05e7965b84bc77
• Download URL:
  https://stacks.cdc.gov/view/cdc/187398/cdc_187398_DS1.pdf
• File Type:
  [PDF - 948.31 KB ]