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Lysophosphatidylcholine aggravates contact hypersensitivity by promoting neutrophil infiltration and IL17 expression.

ABSTRACT: Lysophosphatidylcholine (LPC) is a bioactive lysolipid known to contribute to the development of lung allergic diseases. However, it remains unknown whether LPC possesses proinflammatory properties in the skin as well. Here, we investigated this issue by injection of LPC into the murine contact hypersensitivity (CHS) model induced by 2,4-dinitrofluorobenzene (DNFB). LPC increased the expression of IL17, recruited more neutrophils, and eventually aggravated the CHS in the skins. Moreover, the effects of LPC diminished after neutralizing IL17 or depleting neutrophils. Mechanistically, LPC upregulated not only IL17 but also CXCL1 and CXCL2 in a G2A-dependent manner. Taken together, our study demonstrated that the upregulation of LPC could contribute to allergic skin inflammation by increasing IL17 expression and neutrophil recruitment via G2A receptor. [BMB Reports 2021; 54(4): 203-208].

SUBMITTER: Song MH

PROVIDER: S-EPMC8093940 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Lysophosphatidylcholine aggravates contact hypersensitivity by promoting neutrophil infiltration and IL17 expression.

Song Mi Hye MH Gupta Anupriya A Kim Hye One HO Oh Kwonik K

BMB reports 20210401 4

Lysophosphatidylcholine (LPC) is a bioactive lysolipid known to contribute to the development of lung allergic diseases. However, it remains unknown whether LPC possesses proinflammatory properties in the skin as well. Here, we investigated this issue by injection of LPC into the murine contact hypersensitivity (CHS) model induced by 2,4-dinitrofluorobenzene (DNFB). LPC increased the expression of IL17, recruited more neutrophils, and eventually aggravated the CHS in the skins. Moreover, the eff ...[more]

PMID: 33172544

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Project description:Background: Sustained sleep insufficiency impairs immune system and increases the adverse outcomes of cardiovascular diseases. However, the role and mechanisms prolonged sleep fragmentation (SF) on the outcomes of myocardial infarction (MI) remains elusive. Methods: Among 497 MI patients with complete sleep data participating in the National Health and Nutrition Examination Survey, the association between different types of sleep disorders and post-MI survivability was evaluated. We then developed a mouse model with 10 weeks of SF followed by MI surgery. Emergency hematopoiesis and neutrophil expansion were analyzed. Potential mechanisms were explored using bone marrow (BM) transplantation, anti-SiglecF neutralizing antibodies and Interferon alpha and beta receptor subunit 1 knockout (Ifnar1-/-) in BM. Results: Frequent nocturnal awakening independently predicted reduced survival rate of MI patients, with a hazard ratio (HR) of 2.136 (95% CI=1.142-3.995). Increased infarct size, deteriorated cardiac function and lower survival rate were also observed in MI mice pretreated with 10-week SF. SF facilitated post-MI neutrophil expansion and infiltration into infarct area, differentiating into SiglecFhi subset. Inhibition of SiglecFhi neutrophils allowed for the alleviations of post-MI cardiac remodeling. Furthermore, BM progenitors were skewed toward neutrophil lineage concomitant with the clonal expansion of granulocyte-monocyte progenitors (GMPs) in MI mice pretreated with 10-week SF. Transcriptome analysis and functional experiments revealed that activation of type I interferon (IFN) signaling was involved in this process, while depletion of Ifnar1 in BM and administration of IFNAR1-neutralizing antibodies significantly alleviated post-MI cardiac remodeling and neutrophil expansion. Conclusions: SF aggravates post-MI cardiac remodeling and dysfunction through promoting GMP differentiation and neutrophil expansion. Blockage of type I IFN could alleviate this detrimental influence.

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Lysophosphatidylcholine aggravates contact hypersensitivity by promoting neutrophil infiltration and IL17 expression.

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Lysophosphatidylcholine aggravates contact hypersensitivity by promoting neutrophil infiltration and IL17 expression.

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