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Application of SCGB3A2-PDPN-RhoA signal channel as drug target for inhibiting lung inflammatory factor storm

A signal and inflammation technology, applied in the field of medicine, to achieve the effect of less side effects, alleviation of lung inflammation, and reduction of expression

Active Publication Date: 2021-07-02
SHANGHAI NINTH PEOPLES HOSPITAL SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no application of the SCGB3A2-PDPN-RhoA signaling pathway as a drug target for inhibiting the storm of pulmonary inflammatory factors in the prior art

Method used

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  • Application of SCGB3A2-PDPN-RhoA signal channel as drug target for inhibiting lung inflammatory factor storm
  • Application of SCGB3A2-PDPN-RhoA signal channel as drug target for inhibiting lung inflammatory factor storm
  • Application of SCGB3A2-PDPN-RhoA signal channel as drug target for inhibiting lung inflammatory factor storm

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Santa Cruz anti-PDPN antibody (B-11) prevented excessive production of inflammatory cytokines in primary macrophages in the presence of SCGB3A2.

[0024] Experimental materials: wild-type C57BL / 6 mice were purchased from Shanghai Southern Model Biotechnology Co., Ltd., PDPN antibody (B-11) (product number: sc-166906) was purchased from Santa Cruz Company, TLR2 receptor activator Pam3CSK4 was purchased from InvivoGen Company (product number tlrl-pms), DMEM culture medium was purchased from Gibico Company, and fetal bovine serum was purchased from Hyclone Company. Trizol total RNA extraction reagent, RNA reverse transcriptase and qRT-PCR kit were purchased from Takara Company.

[0025] Experimental method: Isolate primary peritoneal macrophage PEM from wild-type C57BL / 6 mice, inoculate 1 million cells per well into a 12-well plate, and add 1 mL of DMEM medium containing 10% FBS to each well , cultured overnight in an incubator at 37°C with 5% CO2. The next day, macropha...

Embodiment 2

[0028] Streptococcus pneumoniae was used to induce lung inflammatory cytokine storm in wild-type C57BL / 6 mice, and Santa Cruz's PDPN antibody (B-11) was injected into the lungs of mice through the trachea to reduce the production of inflammatory cytokines in the lungs of mice , prolong the survival time of mice, and reduce the infiltration of immune cells in the lungs of mice.

[0029] Experimental materials: wild-type C57BL / 6 mice were purchased from Shanghai Southern Model Biotechnology Co., Ltd., PDPN antibody (B-11) (product number: sc-166906) was purchased from Santa Cruz Company, Streptococcus pneumoniae S.pneumoniae was purchased from ATCC (product number: 6303), and IL-6 ELISA kit were purchased from Invitrogen (product number: 88-7064-22). Trizol total RNA extraction reagent, RNA reverse transcriptase and qRT-PCR kit were purchased from Takara Company.

[0030] Experimental method: the control IgG and PDPN B-11 antibodies were injected into the lungs of mice for thre...

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Abstract

Research finds that exocrine protein SCGB3A2 in lung tracheal bronchus is combined with a receptor PDPN on the cell surface and activates RhoA protein, so that the strength of pneumonia and the expression quantity of inflammatory factors are enhanced, and lung inflammation can be relieved and expression of inflammatory factors and infiltration of lung inflammatory cells can be reduced by blocking combination of SCGB3A2 and PDPN through an antibody. Therefore, the invention provides a brand new target for controlling lung inflammatory factor storm caused by bacteria or viruses. The target spot has a relatively clear signal transmission path, so that the side effect of the medicine for inhibiting the inflammatory factor storm, which is prepared aiming at the target spot, is smaller than that of glucocorticoid.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of the SCGB3A2-PDPN-RhoA signaling pathway as a drug target for inhibiting pulmonary inflammatory factor storm. Background technique [0002] After bacteria or viruses infect the lungs, they can be recognized by the pattern recognition receptors of macrophages in the lungs, and then the pattern recognition receptors will be activated and further activate the transcription factor NF-κB in the cells, thereby activating inflammatory factors such as IL-6, IL-1β and TNFα, these inflammatory factors can further activate other immune cells and regulate the adaptive immune response, thereby helping the body clear infection and repair damaged tissues. Although the inflammatory response is essential to protect the host against infection, excessive activation of inflammatory pathways can produce excess inflammatory cytokines, resulting in an "inflammatory cytokine storm" an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P31/12A61P31/04A61P33/00A61P11/00
CPCA61K45/00A61K39/3955A61P31/12A61P31/04A61P33/00A61P11/00
Inventor 韩磊宋怀东郑翠霞韩兵
Owner SHANGHAI NINTH PEOPLES HOSPITAL SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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