Lub luag haujlwm tshiab rau Mitochondrial Fission hauv Macrophages: Kev Kawm Innate Immunity Induced Los ntawm Beta-glucan
Oct 08, 2023
Nyob rau hauv ib daim ntawv tsis ntev los no luam tawm hauv Nature Immunology, Ding li al. muab kev nkag siab tshiab rau hauv cov txheej txheem ntawm yuav ua li cas kev cob qhia hauv lub cev tiv thaiv kab mob tuaj yeem tshem tawm mob qog noj ntshav. Cov kws sau ntawv tau pom tias cov poov xab tau los ntawm tag nrho cov beta-glucan hais (WGP) tau nce qhov kev teb ntawm lub ntsws interstitial macrophages rau cov qog-derived yam cuam tshuam nrog kev cuam tshuam ntawm cov qog metastasis los ntawm kev txhim kho cytotoxicity rau cov qog nqaij hlav cancer. Cov kws sau ntawv tau txheeb xyuas qhov metabolic sphingolipid-mitochondrial fission axis hauv WGP-kawm macrophages raws li txoj hauv kev tseem ceeb rau qhov tshwm sim no thiab categorized nws raws li ib tug txheej txheem ntawm kev kawm innate tiv thaiv kab mob. [1].
cistanche ntxiv cov txiaj ntsig-nce kev tiv thaiv
Kev lig kev cai, lub cev tsis muaj zog thiab yoog raws lub cev tiv thaiv kab mob sib txawv los ntawm lawv qhov tshwj xeeb thiab lub peev xwm nco. Tau ntev, nws tau xav tias lub cim xeeb ntawm kev tiv thaiv kab mob yog ib qho tshwj xeeb ntawm kev hloov lub cev tiv thaiv kab mob. Ntawm qhov tod tes, innate immune cells tsis tau pom tias yog cov hlwb uas tuaj yeem khaws tau lub cim xeeb phenotype. Nyob rau hauv xyoo tas los no, txawm li cas los xij, qhov kev hloov pauv no tau hloov pauv: cov pov thawj tshwm sim qhia tias qee qhov microbial stimuli thiab endogenous ligands ua rau muaj kev hloov pauv ruaj khov hauv kev ua haujlwm ntawm lub cev tiv thaiv kab mob uas ua rau lawv cov lus teb rau theem nrab stimulation. Cov txheej txheem no tau raug hu ua "kev cob qhia hauv kev tiv thaiv kab mob" lossis "kev tiv thaiv kab mob" [2]. Tom qab thawj zaug kev sib cuag nrog kev cob qhia kev tiv thaiv-inducing stimulus, cov hlwb uas raug cuam tshuam los ntawm metabolic, epigenetic, thiab / los yog transcriptomic reprogramming, uas ua rau muaj zog teb rau qhov kev thuam thib ob.[3, 4].
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Kev cob qhia hauv lub cev tiv thaiv kab mob feem ntau tau piav qhia hauv monocytes thiab macrophages [3] thiab tom qab ntawd hauv granulocytes [5]. Cov hlwb hauv lub cev tiv thaiv kab mob sib qhia muaj peev xwm paub txog thiab teb rau qhov dav dav ntawm stimuli; Txawm li cas los xij, feem ntau cov kev tshawb fawb txog kev tiv thaiv kab mob hauv lub cev tau tsom mus rau Bacille Calmette Guérin (BCG) tshuaj tiv thaiv, qhov tsis muaj zog ntawm Mycobacterium bovis, thiab fungal beta-glucans los ntawm Candida albicans, Trametes versicolor lossis Saccharomyces cerevisiae. Kev cob qhia kev tiv thaiv kab mob hauv lub cev tau tshawb nrhiav hauv kev kho mob ntawm cov kab mob sib kis thiab cov kab mob inflammatory, thaum ua kom muaj kev tiv thaiv kab mob raws li kev kho mob rau kev mob qog noj ntshav tau tshwm sim tsis ntev los no. Piv txwv li, kev txhaj tshuaj BCG tau pom tias muaj cov tshuaj tiv thaiv kab mob rau cov qog nqaij hlav zais zis, melanoma, lymphoma, thiab leukemia. Txawm hais tias beta-glucan kuj tau raug tshaj tawm los ua kom muaj cov nyhuv antitumor ntawm thawj cov qog nqaij hlav subcutaneous [5-7], cov txheej txheem tseeb uas cov lus teb antitumor yog elicited los ntawm kev cob qhia hauv lub cev tiv thaiv kab mob los tswj kev mob qog noj ntshav tsis tau nkag siab zoo. Yog li ntawd, lub luag haujlwm ntawm kev cob qhia kev tiv thaiv kab mob qog noj ntshav thiab nws cov peev xwm kho tau tseem tsis meej.
cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob
Nyem qhov no mus saib Cistanche Enhance Immunity khoom
【Nug ntxiv】 Email: cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692
Cov pab pawg ntawm Jun Yan los ntawm University Louisville Tsev Kawm Ntawv Tshuaj tau ua tiav txoj kev tshawb fawb los tshawb xyuas kev tiv thaiv kev tiv thaiv los ntawm cov poov xab los ntawm WGP hauv macrophages thiab nws cov peev xwm kho mob rau cov kab mob metastatic [1]. Cov kws sau ntawv tau siv qhov kev sim teeb tsa los kawm txog kev mob ntsws ntsws thiab pom tias WGP-kho nas macrophages thiab tib neeg monocytes tau nthuav tawm cov lus teb tau txais txiaj ntsig zoo raws li kev sib cuag ncaj qha nrog cov qog hlwb lossis raug rau cov qog-derived soluble yam, xws li macrophage migration inhibitory factor (MIF) . Qhov tseem ceeb, WGP tuaj yeem ua rau muaj kev tiv thaiv kev tiv thaiv hauv vivo, nce kev tsim cov hlwb myeloid hauv cov pob txha pob txha yam tsis muaj kab mob hauv cov ntaub so ntswg. Piv txwv li, WGP-kho nas lossis nas nrog cov pob txha rov ua dua los ntawm cov nas uas tau kawm WGP tau ua kom muaj sia nyob ntev thiab txo cov qog nqaij hlav hauv lub ntsws tom qab txhaj tshuaj ntawm cov qog nqaij hlav hauv lub ntsws los yog hauv K-rasLA1 nas nrog kev loj hlob ntawm lub ntsws cancer. Interestingly, WGP-mediated kev cob qhia thiab metastasis tswj tau qhia meej meej nrog kev ua haujlwm ntawm lub ntsws interstitial macrophages los ntawm cov pob txha pob txha tab sis tsis yog alveolar macrophages thiab tsis nyob ntawm neutrophils lossis B thiab T hlwb, uas tau ua kom pom zoo los ntawm kev siv neutralizing thiab depletion. txoj hauv kev hauv ntau cov qauv qog. Txawm li cas los xij, WGP-mediated kev cob qhia txhim kho T-cell cov lus teb hauv cov qog nqaij hlav nas vim qhov txo qis ntawm kev tswj T hlwb, txo qis zaus ntawm PD-1-CD zoo4+ thiab CD8+ T. hlwb, thiab ntau lawm ntawm T-cell-derived TNF-. Tsis tas li ntawd, kev saws me nyuam hauv vitro WGP-kev cob qhia cov pob txha pob txha-derived macrophages (BMDMs) rau hauv cov nas uas tsis paub qab hau uas tau hloov pauv nrog cov qog nqaij hlav cancer hauv lub ntsws ua rau txo cov qog nqaij hlav hauv lub ntsws, qhia txog kev siv BMDMs uas tau txais kev cob qhia los ntawm tes. kho mob cancer. Txhawm rau ntsuas qhov muaj peev xwm kho mob ntxiv, cov kws sau ntawv siv ntau tus qauv kab mob metastatic nas thiab pom tau tias melanoma thiab mob qog noj ntshav hauv lub ntsws metastasis hauv lub ntsws thiab kev nthuav tawm ntawm cov qog ntshav qog ntshav hauv lub siab tau txo qis hauv WGP-kho nas, hais txog cov txiaj ntsig ntawm kev kawm. kev tiv thaiv kom zoo tswj lub ntsws qog thiab metastasis (Daim duab 1).
Ding et al. ua qhov kev tshawb fawb ntxaws heev rau cov txheej txheem molecular hauv qab WGP-mediated kev cob qhia hauv macrophages.
Daim duab 1 Macrophages tau kawm nrog tag nrho beta-glucan hais (WGP) inhibit qog metastasis. Interstitial ntsws macrophages originating los ntawm cov pob txha pob txha tuaj yeem betrained nrog WGP nyob rau hauv vivo thiab txhim kho kev teb rau cov qog hlwb los yog soluble qog-derived yam. Raws li qhov tshwm sim, kev kawm macrophages inhibit ntsws metastasis vim kev txhim kho TNF- ntau lawm, nce phagocytosis thiab cytotoxicity rau cov qog hlwb, thiab kev hloov kho ntawm T-cell teb. Kev cob qhia kev tiv thaiv kab mob hauv lub cev yog kho los ntawm kev txhim kho kev sib txuas ntawm sphingolipids thiab tom qab sib sau ntawm S1P hauv macrophages, ua rau Drp1- tswj mitochondrial fission, uas yuav tsum tau ua kom muaj zog mitochondrial ROS ntau lawm thiab ua pa, ntxiv rau cytotoxicity thiab TNF. ntau lawm
Lawv tau pom tias WGP tau nce qhov tsim ntawm TNF- hauv ntsws interstitial macrophages thiab txhim kho lawv lub peev xwm phagocytic thiab cytotoxicity rau cov qog hlwb. Qhov zoo siab, yav dhau los txoj kev tshaj tawm koom nrog hauv kev txhawb nqa kev tiv thaiv kab mob, suav nrog mTOR/HIF-1 lossis Nlrp3 inflammasome thiab IL-1 /IL-1R txoj hauv kev [4], tsis tau ua lub luag haujlwm hauv WGP-mediated kev cob qhia ntawm macrophages. Hloov chaw, txoj kev sphingolipid-mediated mitochondrial fission pathway yog lub luag haujlwm rau WGP-induced cob qhia kev tiv thaiv kab mob hauv macrophages thiab kev tswj hwm ntawm metastasis. Cov metabolite sphingosine-1-phosphate (S1P) txhim kho kev ua pa muaj peev xwm thiab mtROS ntau lawm hauv WGP-kawm macrophages thiab nce lawv qhov sib txawv, tsiv teb tsaws, thiab muaj sia nyob. Qhov zoo siab, dynamin ntsig txog cov protein-1 (Drp1) tau xav tau rau cov lus teb ua haujlwm no thiab qhib los ntawm S1P. Lub xub ntiag ntawm S1P - Drp1 txoj hauv kev ua rau mitochondrial fission yav dhau los tau piav qhia hauv T hlwb [8]. Cov kev tshawb pom no qhia tias mitochondrial fission yog qhov tseem ceeb rau WGP-induced kawm tiv thaiv kab mob ntawm macrophages, uas ua rau muaj kev tiv thaiv, tsawg kawg yog ib feem, ntawm cov kab mob metastatic (Fig. 1).
cistanche ntxiv cov txiaj ntsig-nce kev tiv thaiv
Hauv cov ntsiab lus, Ding et al. nrhiav tau ib lub tswv yim tshiab rau kev kawm tiv thaiv kab mob hauv macrophages induced los ntawm WGP nrog rau kev kho mob ntawm thawj thiab metastatic qog. Cov tswv yim no yuav tsim nyog rau cov neeg mob uas xav tau kev kho mob ntxiv los tiv thaiv qhov tshwm sim ntawm lub ntsws metastasis. Tam sim no, txawm li cas los xij, nws tseem tsis tau paub meej tias WGP-tsim kev tiv thaiv kab mob kuj tseem tuaj yeem tiv thaiv kev sib kis ntawm cov qog nqaij hlav cancer hauv lwm lub cev. Muab ntau thiab ntau qhov chaw thiab kev ua tiav ntawm beta-glucan, ib qho ntawm cov kev nyuaj siab tshaj plaws yog cov qauv ntawm cov molecules tsim nyog rau kev siv tshuaj kho mob. Ntawm qhov tod tes, nce mitochondrial fission thiab ua pa muaj peev xwm ua tau tiav los ntawm cov tshuaj tshwj xeeb [9]. Ntxiv mus, qhov tsub zuj zuj ntawm S1P kuj yuav ua tiav los ntawm kev siv doxorubicin [10]. Cov kev siv tshuaj kho mob zoo li no yuav yog cov tswv yim nthuav dav rau yav tom ntej rau kev ua kom lub cim xeeb hauv lub cev hauv macrophages, uas tuaj yeem tsim tawm ntawm lub txee rau kev siv cell kho tiv thaiv kab mob.
Cov txiaj ntsig ntawm cistanche tubulosa-Antitumor
REFERENCES
1. Ding C, Shrestha R, Zhu X, Geller AE, Wu S, Woeste MR, et al. Inducing kev tiv thaiv kab mob hauv pro-metastatic macrophages los tswj cov qog metastasis. Nat Immunol. 2023; 24:239–54. https://doi.org/10.1038/s41590-022-01388-8
2. Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, et al. Txhais kev tiv thaiv kev tiv thaiv thiab nws lub luag haujlwm hauv kev noj qab haus huv thiab kab mob. Nat Rev Immunol. 2020; 20:375–88. https://doi.org/10.1038/s41577-020-0285-6
3. Saeed S, Quintin J, Kerstens HHD, Rao NA, Aghajanirefah A, Matarese F, et al. Epigenetic programming ntawm monocyte-rau-macrophage sib txawv thiab kev cob qhia innate tiv thaiv. Kev tshawb fawb. Xyoo 2014; 345: 1251086. https://doi.org/10.1126/science.1251086
4. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. MTOR thiab HIF-1 - nruab nrab aerobic glycolysis ua lub hauv paus metabolic rau kev tiv thaiv kab mob. Kev tshawb fawb. Xyoo 2014; 345: 1250684. https://doi.org/10.1126/science.1250684
5. Kalafati L, Kourtzelis I, Schulte-Shrepping J, Li X, Hatzioannou A, Grinenko T, et al. Innate kev tiv thaiv kab mob ntawm granulopoiesis txhawb kev tiv thaiv qog nqaij hlav. Cell. 2020; 183:771–785.e12. https://doi.org/10.1016/j.cell.2020.09.058
6. Geller A, Shrestha R, Yan J. Poov-derived -glucan hauv kev mob qog noj ntshav: siv cov tshuaj kho mob tshiab. Int J Mol Sci 2019; 20:3618. https://doi.org/10.3390/ijms20153618
7. Priem B, van Leent MMT, Teunissen AJP, Sofias AM, Mouris VP, Willemsen L, et al. Kev cob qhia kev tiv thaiv-txhim kho nanobiologic therapy inhibits qog loj hlob thiab potentiates checkpoint inhibition. Cell. 2020; 183:786–801.e19. https://doi.org/10.1016/j.cell.2020.09.059
8. Tian L, Wu Y, Choi HJ, Sui X, Li X, Sofi MH, et al. S1P / S1PR1 signaling sib txawv tswj cov lus teb allogeneic ntawm CD4 thiab CD8 T hlwb los ntawm kev hloov kho mitochondrial fission. Cell Mol Immunol. 2022; 19:1235–50. https://doi.org/10.1038/s41423-022-00921
9. Singh A, Facenda D, Campanella M. Pharmacological kev nce qib hauv kev kho mitochondrial. EBioMedicine. 2021; 65:103244. https://doi.org/10.1016/j.ebiom.2021.103244
10. Bonica J, Clarke CJ, Obeid LM, Luberto C, Hannun YA. Upregulation ntawm sphingosine kinase 1 nyob rau hauv teb rau doxorubicin generates angiogenic teb los ntawm stabilization ntawm Snail. FASEB J. 2023; 37:e22787. https://doi.org/10.1096/fj.202201066R
