Interleukin-11 Receptor Subunit A-1 Is Required for Maximal Airway Responsiveness to Methacholine After Acute Exposure to Ozone

Details

• Personal Author:
  Atkins CL ; Haque IU ; Jackson WT ; Johnston RA ; Kashon ML ; Mitchell NC ; Pilkington AW 4th ; Siddiqui SR ; Spencer CY
• Description:
  Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit a-1 (IL-11Ra1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Ra1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Ra1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O3), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O3, we assessed lung inflammation and airway responsiveness in wild-type and IL-11Ra1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O3-exposed IL-11Ra1-deficient as compared with O3-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O3-exposed mice. However, airway responsiveness to acetyl-beta-methylcholine chloride (methacholine) was significantly diminished in IL-11Ra1-deficient as compared with wild-type mice after O3 exposure. In conclusion, these results demonstrate that IL-11Ra1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Immune System Lung Occupational Health Ozone Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Airway Hyperresponsiveness Animal Author Keywords: Adiponectin Cell Signaling Cellular Effects Coefficient Of Lung Tissue Elastance Cytokines Genetic Factors Immune Reaction Interleukin-11 Lung Irritants Respiratory Diseases Studies

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• ISSN:
  0363-6119
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  323
• Issue:
  6
• NIOSHTIC Number:
  nn:20066522
• Citation:
  Am J Physiol Regul Integr Comp Physiol 2022 Dec; 323(6):R921-R934
• Contact Point Address:
  Richard A. Johnston, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia
• Email:
  rfj1@cdc.gov
• CAS Registry Number:
  Methacholine (CAS RN 55-92-5) ; Ozone (CAS RN 10028-15-6)
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4ea65477314986d813855f1746223a837dce19bfeae6d36387e936cbce33cd08f14ae654aa0b21653e9a821dc22124bf571db2c3f0c2f61deb5cf8fcaa69e796
• Download URL:
  https://stacks.cdc.gov/view/cdc/231105/cdc_231105_DS1.pdf
• File Type:
  [PDF - 1.13 MB ]