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Trypsin may induce cytokine storm in M1 macrophages, resulting in critical coronavirus disease

Hongyu Chen1, Shirong Huang2, Qingquan Chen2

  • 1Zhongwei Tech Innovation Medical Research Institute Co., Ltd. Beijing 100000, China.

Respiratory Physiology & Neurobiology
|May 17, 2022
PubMed

Insights

Trypsin, a PAR2 activator, may facilitate coronavirus transmission by upregulating IL-17 and activating macrophages. This suggests a novel pathway for viral spread in patients.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Interleukin-17 (IL-17) signaling in airway epithelial cells amplifies inflammation.
  • The cell-to-cell spread of coronaviruses remains incompletely understood.
  • Trypsin acts as a protease-activated receptor-2 (PAR2) activator, influencing inflammatory pathways.

Purpose of the Study:

  • To investigate the potential role of trypsin in coronavirus activation and transmission.
  • To explore the in vitro and in vivo effects of trypsin on coronavirus-related cellular responses.

Main Methods:

  • Overexpression of trypsin in A549 cells.
  • Analysis of IL-17 and angiotensin-converting enzyme (ACE) levels.
  • Assessment of trypsin's effect on M1 macrophages in humanized transgenic mice.

Main Results:

  • Trypsin overexpression in A549 cells led to increased IL-17 and ACE levels.
  • Trypsin was found to activate M1 macrophages in humanized transgenic mice.
  • The study did not observe modifications in metapneumovirus growth kinetics due to trypsin.

Conclusions:

  • Upregulation of trypsin may represent a novel pathway supporting coronavirus transmission.
  • Trypsin's activation of IL-17 and macrophages could contribute to viral spread.
  • Further research is warranted to elucidate trypsin's precise role in coronavirus pathogenesis.
Keywords:
CytokinesMacrophagesSARS-Cov-2Trypsin

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