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TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells.

Immunity | 2018

Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages decreased intestinal motility and was sufficient to reverse the GI hypermotility that is associated with chemotherapy treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of prostaglandin E2 and elicited colon contraction in a paracrine manner via prostaglandin E receptor signaling in intestinal smooth muscle cells without input from the enteric nervous system. Collectively, our data identify TRPV4-expressing MMs as an essential component required for maintaining normal GI motility and provide potential drug targets for GI motility disorders.

Pubmed ID: 29958798 RIS Download

Additional research tools detected in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NIAMS NIH HHS, United States
    Id: K08 AR065577
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM101218
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR070116
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK103901
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK095867
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK052574

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