NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG

Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found t...

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Veröffentlicht in:International immunopharmacology 2024-01, Vol.126, p.111257-111257, Article 111257
Hauptverfasser: Mi, Yingqian, Tang, Mengyan, Wu, Qiong, Wang, Yinan, Liu, Qihui, Zhu, Pei, Xue, Xiaoyang, Liu, Yuntong, Chai, Xinyu, Hou, Yuyang, Yan, Dongmei
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container_title International immunopharmacology
container_volume 126
creator Mi, Yingqian
Tang, Mengyan
Wu, Qiong
Wang, Yinan
Liu, Qihui
Zhu, Pei
Xue, Xiaoyang
Liu, Yuntong
Chai, Xinyu
Hou, Yuyang
Yan, Dongmei
description Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found that BCG could stimulate mice BMDM to the M1 type and kill tumor cells. After the deletion of NMAAP1, the tumor volume of mice became larger, and the number of M1 type macrophages in the tumor decreased significantly. When macrophages were induced into the M1 type, aerobic glycolysis, the Warburg effect manifested in the increased uptake of glucose and the conversion of pyruvate to lactic acid. NMAAP1 could bind with IP3R and regulate macrophage polarization to the M1 type. However, the specific mechanism of how NMAAP1 regulates macrophage polarization towards the M1 type and plays an antitumor role must be clarified. NMAAP1 could promote the release of lactic acid and pyruvate, enhance the glycolysis of macrophages, and affect the expression of HIF-1α. After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca /NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. NMAAP1 promotes the polarization of macrophages towards the M1 type by affecting the Warburg effect stimulated by BCG.
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Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found that BCG could stimulate mice BMDM to the M1 type and kill tumor cells. After the deletion of NMAAP1, the tumor volume of mice became larger, and the number of M1 type macrophages in the tumor decreased significantly. When macrophages were induced into the M1 type, aerobic glycolysis, the Warburg effect manifested in the increased uptake of glucose and the conversion of pyruvate to lactic acid. NMAAP1 could bind with IP3R and regulate macrophage polarization to the M1 type. However, the specific mechanism of how NMAAP1 regulates macrophage polarization towards the M1 type and plays an antitumor role must be clarified. NMAAP1 could promote the release of lactic acid and pyruvate, enhance the glycolysis of macrophages, and affect the expression of HIF-1α. After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca /NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. 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After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca /NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. NMAAP1 promotes the polarization of macrophages towards the M1 type by affecting the Warburg effect stimulated by BCG.</description><subject>Animals</subject><subject>BCG Vaccine</subject><subject>Glycolysis</subject><subject>Lactic Acid - metabolism</subject><subject>Macrophage Activation</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Pyruvates - pharmacology</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1OwzAQhC0EoqXwBgj5yCXBa8c_OZYKClILHODCxXIdJ02VNCFOhMLTkyqF065WM7O7H0LXQEIgIO52Yb5v87IOKaEsBADK5QmagpIqAEn46dBzIQMuRTxBF97vCBnmEZyjCZOxUjGQKfp8Wc_nb4Abl3WFaV2CS2Obqt6azOG6KkyT_-TVHg-7KrwG3Pa1w-22qbpsi7Oit1XR-9xjP5xyDPjO2y2-Xywv0VlqCu-ujnWGPh4f3hdPwep1-byYrwLLiGyDmAAo6wR1yYZwCzxhjFFpJbEmjZSNbOp4JIWUUm0iCcQpymE43xFrqVBshm7H3LqpvjrnW13m3rqiMHtXdV5TFVMhCGNikEajdHjR-8alum7y0jS9BqIPVPVOj1T1gaoeqQ62m-OGblO65N_0h5H9Av3ZdK4</recordid><startdate>20240105</startdate><enddate>20240105</enddate><creator>Mi, Yingqian</creator><creator>Tang, Mengyan</creator><creator>Wu, Qiong</creator><creator>Wang, Yinan</creator><creator>Liu, Qihui</creator><creator>Zhu, Pei</creator><creator>Xue, Xiaoyang</creator><creator>Liu, Yuntong</creator><creator>Chai, Xinyu</creator><creator>Hou, Yuyang</creator><creator>Yan, Dongmei</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0003-2589-1778</orcidid><orcidid>https://orcid.org/0000-0002-6489-239X</orcidid><orcidid>https://orcid.org/0000-0002-8314-491X</orcidid></search><sort><creationdate>20240105</creationdate><title>NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG</title><author>Mi, Yingqian ; Tang, Mengyan ; Wu, Qiong ; Wang, Yinan ; Liu, Qihui ; Zhu, Pei ; Xue, Xiaoyang ; Liu, Yuntong ; Chai, Xinyu ; Hou, Yuyang ; Yan, Dongmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c307t-90118ce62edb05c15d33327c70caf48c4cfe54767778b4710e8251889e0cc2683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>BCG Vaccine</topic><topic>Glycolysis</topic><topic>Lactic Acid - metabolism</topic><topic>Macrophage Activation</topic><topic>Macrophages</topic><topic>Mice</topic><topic>Pyruvates - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mi, Yingqian</creatorcontrib><creatorcontrib>Tang, Mengyan</creatorcontrib><creatorcontrib>Wu, Qiong</creatorcontrib><creatorcontrib>Wang, Yinan</creatorcontrib><creatorcontrib>Liu, Qihui</creatorcontrib><creatorcontrib>Zhu, Pei</creatorcontrib><creatorcontrib>Xue, Xiaoyang</creatorcontrib><creatorcontrib>Liu, Yuntong</creatorcontrib><creatorcontrib>Chai, Xinyu</creatorcontrib><creatorcontrib>Hou, Yuyang</creatorcontrib><creatorcontrib>Yan, Dongmei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mi, Yingqian</au><au>Tang, Mengyan</au><au>Wu, Qiong</au><au>Wang, Yinan</au><au>Liu, Qihui</au><au>Zhu, Pei</au><au>Xue, Xiaoyang</au><au>Liu, Yuntong</au><au>Chai, Xinyu</au><au>Hou, Yuyang</au><au>Yan, Dongmei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2024-01-05</date><risdate>2024</risdate><volume>126</volume><spage>111257</spage><epage>111257</epage><pages>111257-111257</pages><artnum>111257</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. 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subjects Animals
BCG Vaccine
Glycolysis
Lactic Acid - metabolism
Macrophage Activation
Macrophages
Mice
Pyruvates - pharmacology
title NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG
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