Motile Cilia Harbor Serum Response Factor as a Mechanism of Environment Sensing and Injury Response in the Airway

Details

• Personal Author:
  Bailey KL ; Heires AJ ; Nordgren TM ; Poole JA ; Romberger DJ ; Sisson JH ; Sweeter J ; Wyatt TA ; Bailey KL ; Heires AJ ; Nordgren TM ; Poole JA ; Romberger DJ ; Sisson JH ; Sweeter J ; Wyatt TA
• Description:
  Nonmotile primary cilia are recognized as important sensory organelles during development and normal biological functioning. For example, recent work demonstrates that transcriptional regulators of the sonic hedgehog signaling pathway localize to primary cilia and participate in sensing and transducing signals regarding the cellular environment. In contrast, motile cilia are traditionally viewed as mechanical machinery, vital for the movement of solutes and clearance of bacteria and debris, but not participants in cellular sensing and signaling mechanisms. Recently, motile cilia were found to harbor receptors responsible for sensing and responding to environmental stimuli. However, no transcription factors are known to be regulated by cilia localization as a sensing mechanism in vertebrates. Using a mouse model of organic dust-induced airway inflammation, we found that the transcription factor serum response factor (SRF) localizes to motile cilia of airway epithelial cells and alters its localization in response to inflammatory stimuli. Furthermore, inhibition of SRF signaling using the small molecule CCG-1423 reduces organic dust-induced IL-8 release from bronchial epithelial cells and stimulates cilia beat frequency in ciliated mouse tracheal epithelial cells. Immunohistochemical analyses reveal that SRF localizes to the cilia of mouse brain ependymal and ovarian epithelial cells as well. These data reveal a novel mechanism by which a transcription factor localizes to motile cilia and modulates cell activities including cilia motility and inflammation response. These data challenge current dogma regarding motile cilia functioning and may lead to significant contributions in understanding motile ciliary signaling dynamics, as well as mechanisms involving SRF-mediated responses to inflammation and injury. [Description provided by NIOSH]
• Subjects:
  Animals Dust Immune System Lung Occupational Health Respiratory System Safety
• Keywords:
  Airway Inflammation Animal Studies Author Keywords: Serum Response Factor Cellular Effects Cellular Function Immune Reaction Lung Cells Motile Cilia Organic Dust Organic Dusts Physiological Response Signaling Pathways

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  306
• Issue:
  9
• NIOSHTIC Number:
  nn:20053151
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2014 May; 306(9):L829-L839
• Contact Point Address:
  D. J. Romberger, 988090 Nebraska Medical Center, Omaha, NE 68198
• Email:
  dromberg@unmc.edu
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Agriculture, Forestry and Fishing ; Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6733901e0661732e8226d9065da517753bdf8f8f076caf1a52e9bcc10dfee9658fec59e7f5dfbf0a15b3e777bfe4aef933a07ab40f111ddcf765fec01ea50758
• Download URL:
  https://stacks.cdc.gov/view/cdc/215965/cdc_215965_DS1.pdf
• File Type:
  [PDF - 2.41 MB ]