Kev Tiv Thaiv: Suav Cov Neeg Tshawb Fawb Tau Pom Tias Tias Lub Hom Phiaj Roj Muaj Kab Mob Choj Ntsig hauv Macrophages tuaj yeem tshem cov kab mob sib kis

Cov ntawv pov thawj tsis ntev los no qhia txog qhov sib txuas ntawm cov roj metabolism hauv lub cev thiab lub cev tsis muaj zog. Tom qab kis tus kab mob, macrophages pom tias txo cov roj synthesis thiab cov lus qhia tawm tsam tus kab mob antiviral nrog rau IFN-I. IFN-1 tuaj yeem ua rau qhov kev txuam ntau ntawm 25 hydroxycholesterol, uas yuav tiv thaiv kom tsis txhob muaj qhov ntxeem tau ntawm tus kab mob. Txawm li cas los xij, nws tsis paub meej tias lwm cov roj ntsha ntsig txog cov tshuaj tiv thaiv metabolites lossis cov enzymes tswj qhov tsis muaj zog hauv lub cev.

Hauv txoj kev tshawb nrhiav tshiab, Wang Hongyan, pab pawg tshawb fawb ntawm lub chaw nruab nrab ntawm molecular cell science zoo tshaj thiab kev hloov kho tshiab, Lub Koom Haum ntawm Biochemistry thiab cell biology, Suav Academy ntawm Science, thiab Wei bin, tus xibfwb ntawm Shanghai University, tau ua haujlwm ua ke los tshuaj ntsuam qhov pom tseeb. qib ntawm ntau yam ntawm cov enzymes los tswj cov metabolism hauv cov roj cholesterol kom nkag siab zoo ntxiv txog seb cov roj ntsha tiv thaiv kab mob sib kis tau li cas. Cov kev tshawb fawb ntsig txog tshawb fawb tau tsis ntev los no tau tshaj tawm hauv phau ntawv Journal of immunology. Cov npe ntawm daim ntawv yog "tsom rau 7-dehydrocholesterol txo kev sib xyaw ua ke cov roj (metabolism) thiab cov IRF3 ua kom ua tiav kom sib kis".

Kev Tiv Thaiv, 2019, doi: 10.1016 / j.immuni.2019.11.015

Txhawm rau kom nrhiav cov enzymes koom nrog kev tiv thaiv kab mob los tiv thaiv lossis sib luag roj cov roj ntsha tiv thaiv kab mob, cov kws tshawb fawb soj ntsuam cov noob sib txawv hauv daim siab mob los ntawm cov neeg mob kis tus kab mob siab B (HBV) thiab nas muaj tus kab mob vesicular stomatitis (VSV).

7-dehydrocholesterol reductase (DHCR7) yog ib qho enzyme uas hloov 7-dehydrocholesterol (7-DHC) rau cov roj (cholesterol). Cov neeg mob nrog DHCR7 hloov pauv tau muaj kev puas siab puas ntsws. Txawm li cas los xij, lub luag haujlwm ntawm DHCR7 hauv kev tiv thaiv innate tsis meej. Qhov kev tshawb nrhiav tshiab no qhia tau hais tias kev tawm ntawm DHCR7 gene lossis DHCR7 inhibitor kev kho mob tuaj yeem txhawb txoj kev ua haujlwm ntawm IRF3 thiab kev tsim cov tshuaj interferon I (IFN β), thiaj li tshem tawm ntau cov kab mob hauv vivo lossis hauv vitro.

Qhov zoo li, tamoxifen, yog ib qho kev siv tshuaj kho mob siv los kho mob cancer ntawm lub mis, tau pom zoo los ntawm Asmeskas Cov Khoom Noj thiab Tshuaj (FDA) los tswj cov kev ua haujlwm ntawm enzyme ntawm DHCR7.

Txoj kev tshawb nrhiav tshiab kuj tau qhia tias kev kho tamoxifen tiv thaiv kev tiv thaiv tus kab mob VSV thiab Zika ntawm qib ntawm cev, qhia tias tamoxifen yuav raug siv los ua ib qho tshuaj tiv thaiv kev tiv thaiv. Ntshav dej 7-DHC cov nas ntawm cov nas kho nrog AY9944, tus DHCR7 inhibitor, nce ntau, uas txhawb cov phosphorylation ntawm IRF3 thiab tsim cov khoom ntawm IFN β hauv macrophages, yog li tiv thaiv cov nas los ntawm kev txhaj tshuaj tiv thaiv tus kabmob VSV lossis H1N1.

Tsis tas li ntawd, txoj kev tshawb pom tshiab pom tias tus kab mob kis tus kab mob txhim kho Akt3 qhia, thaum kho 7-DHC kho ntxiv Akt3. Akt3 khi IRF3 ncaj qha thiab tsim IRF3 phosphorylation ntawm ser385 qhov chaw ntawm IRF3. Tsis tas li ntawd, tbk1 ntxias IRF3 phosphorylation ntawm ser386 qhov chaw ntawm IRF3, thiaj li paub qhov dimerization thiab tag nrho kev ua haujlwm ntawm IRF3.

Tag nrho txhua qhov, qhov kev tshawb pom tshiab no qhia tau tias cov khoom nruab nrab ntawm cov khoom siv roj cholesterol, 7-DHC thiab DHCR7 inhibitors, tuaj yeem txhawb nqa ifn-1 ntau lawm thiab tiv thaiv cov lus teb los ntawm kev ua kom muaj Akt3 thiab IRF3. Qhov kev tshawb pom no tuaj yeem pab txhawb kev tsim cov tshuaj tshiab rau kev kho mob kis kab mob. Txoj kev tshawb fawb tshiab no tseem muaj kev nkag siab tshiab txog yuav ua li cas cov roj (metabolism) roj ua rau muaj kev tiv thaiv tsis muaj zog.

Siv:

1.Jun Xiao et al, Kev Cuam Tshuam 7-Dehydrocholesterol Reductase ua ke nrog Cholesterol Cov Hluav Taws Xob thiab IRF3 Kev Ua Kom Yooj Yim rau Kev Tshem Tawm Kom Tsis Muaj Kab Mob, Kuaj (2019). DOI: 10.1016 / j.immuni.2019.11.015.

2.Txoj roj cholesterol metabolism hauv macrophages kom tshem tawm kab mob kis mob https://medicalxpress.com/news/2019-12-cholesterol-metabolism-macrophages-viral-infection.html