Kodi LL-37 ndi chiyani ndipo imachita chiyani?

Mawu ofunika：LL-37,154947-66-7,LL-37 Peputi

M'malo ovuta a chitetezo chamthupi chamunthu, mamolekyu ochepa amakhala osunthika komanso ovuta ngati LL-37. Monga munthu yekhayo m'gulu la cathelicidin la antimicrobial peptides (AMPs),LL-37amagwira ntchito ngati woteteza kutsogolo ku matenda, wowongolera chitetezo chamthupi, komanso wothandizira kukonza minofu ndi kusintha kwa matenda. Kapangidwe kake kapadera ndi ntchito zambiri zapangitsa kuti ikhale yofunika kwambiri pakufufuza za chitetezo chamthupi, tizilombo toyambitsa matenda, ndi mankhwala azachipatala - zomwe zimakhudzanso kuchiza matenda, matenda otupa, komanso khansa. M'munsimu, ife timaphwanya ndendende zomweLL-37ndi, momwe zimagwirira ntchito, ndi chifukwa chake zili zofunika, mothandizidwa ndi kafukufuku wowunikiridwa ndi anzawo ndikukonzedwa kuti ziwonekere pakufufuza.

Kodi LL-37 Ndi Chiyani Kwenikweni? Choyambirira pa Mapangidwe Ake ndi Chiyambi Chake

LL-37ndi peptide yaing'ono, cationic (positively charged)-kutanthauza kuti imakhala ndi magetsi abwino pa pH ya thupi-yomwe imakhala ndi gawo losakambitsirana mu chitetezo cha mthupi chachibadwa, mzere woyamba wa chitetezo ku tizilombo toyambitsa matenda tisanalowe. (chidule cha “L”), motero “LL-37.” Mosiyana ndi mamolekyu ambiri a chitetezo chamthupi omwe amapangidwa ndi maselo apadera a chitetezo chamthupi, LL-37 imapangidwa ndi mitundu yosiyanasiyana ya maselo, ndikupangitsa kuti ikhalepo ponseponse muzotchinga zam'thupi komanso ma netiweki a chitetezo chamthupi.

LL-37sichimapangidwa mu mawonekedwe ake ogwira ntchito; m'malo mwake, amapangidwa ngati puloteni yoyambilira yotchedwa hCAP18 (protein cationic antimicrobial protein 18), yomwe imasungidwa m'maselo a chitetezo cha mthupi monga ma neutrophils ndi macrophages, komanso m'maselo otchinga monga omwe amakhala pakhungu, mapapo, matumbo, ndi mkodzo. Thupi likawona chowopsa-monga matenda a bakiteriya, kuwonongeka kwa minofu, kapena kutupa-hCAP18 imadulidwa kunja ndi ma enzyme otchedwa proteases, kutulutsa LL-37 peptide yogwira ntchito. Mwachindunji, LL-37 imapanga amphipathic α-helix, mawonekedwe omwe mbali imodzi ya peptide ndi hydrophobic (madzi othamangitsa madzi) ndipo ina ndi hydrophilic (madzi okopa) komanso ovomerezeka. Kapangidwe kapadera kameneka ndikofunika kwambiri pa ntchito yake: mbali ya hydrophobic imalola kuti igwirizane ndi lipid nembanemba za tizilombo toyambitsa matenda, pamene mbali yabwinoyi imathandiza kuti imangirire kumalo osokonezeka a mabakiteriya, mavairasi, ndi bowa.

Kafukufuku watsimikizira kuti mapangidwe a LL-37 ndi ofunika pa ntchito yake; kusinthidwa kulikonse pamatsatidwe ake a amino acid kapena mawonekedwe a helical kumasokoneza kwambiri kuthekera kwake kulimbana ndi tizilombo toyambitsa matenda ndikuwongolera chitetezo chokwanira (Sørensen OE, et al., 2001). 

Ntchito Zazikulu za LL-37: Kupitilira Ntchito Yopha tizilombo

PameneLL-37amadziwika kwambiri chifukwa cha mphamvu yake yopha tizilombo toyambitsa matenda, ntchito yake m'thupi imapitirira kuposa chitetezo chosavuta cha antimicrobial. Imakhala ngati "mpeni wankhondo waku swiss" wa chitetezo chamthupi, chokhala ndi ntchito zomwe zimatha kuwongolera matenda, kusinthasintha kwa chitetezo chamthupi, kukonza minofu, komanso antitumor. Iliyonse mwa ntchitozi imalumikizidwa, kupangitsa LL-37 kukhala chowongolera chofunikira cha homeostasis yonse ya thupi.

Ntchito yoyamba yaLL-37ndi ntchito yake yolimbana ndi tizilombo toyambitsa matenda, kutanthauza kuti ikhoza kuyang'ana ndi kuthetsa tizilombo toyambitsa matenda osiyanasiyana, kuphatikizapo mabakiteriya, mavairasi, bowa, ngakhalenso biofilms-midzi ya mabakiteriya omwe amapanga chitetezo chotetezera ndipo sagonjetsedwa ndi maantibayotiki. Mapangidwe ake a amphipathic α-helix amalola kuti amangirire ku tizilombo toyambitsa matenda (omwe ali olemera mu anionic lipids), kumene amapanga pores kapena kusokoneza umphumphu wa nembanemba, zomwe zimatsogolera ku selo lysis (kuphulika) ndi imfa. Njira imeneyi imagwira ntchito polimbana ndi mabakiteriya a Gram-positive (monga Staphylococcus aureus ndi Streptococcus pneumoniae) ndi mabakiteriya a gram-negative (monga Escherichia coli ndi Pseudomonas aeruginosa),LL-37chida champhamvu cholimbana ndi matenda a bakiteriya.

PameneLL-37imatha kulimbana ndi tizilombo toyambitsa matenda mwachindunji, imathandizanso kwambiri pakuwongolera chitetezo chamthupi, kuwonetsetsa kuti mayankho otupa amakhala oyenera - osati ofooka kwambiri (kulola kuti matenda apitirire) kapena amphamvu kwambiri (kuyambitsa kuwonongeka kwa minofu). Njirayi, yotchedwa immunomodulation, imapangitsa LL-37 kukhala wosewera wamkulu pazovuta zonse komanso zotupa zosatha.

Mu kutupa kwakukulu (monga komwe kumayambitsidwa ndi kudulidwa kapena matenda), LL-37 imakhala ngati molekyulu yowonongeka: imatenga maselo a chitetezo cha mthupi monga ma neutrophils, monocytes, ndi T maselo kumalo a matenda kapena kuwonongeka, kuwatsogolera kumene akufunikira kwambiri. Zimalimbikitsanso kupanga ma cytokines oyambitsa kutupa-mamolekyu omwe amachititsa kuti chitetezo cha mthupi chitetezeke-monga interleukin-8 (IL-8) ndi monocyte chemoattractant protein-1 (MCP-1), yomwe imathandizira kuchotsa tizilombo toyambitsa matenda ndi kuyambitsa kukonza minofu.

Kukonza Tissue ndi Angiogenesis: Kuchiritsa Mafupa Owonongeka

Kuphatikiza pa ntchito zake zolimbitsa thupi,LL-37imathandiza kwambiri kukonza minofu ndi kuchiritsa mabala. Minofu ikawonongeka-kaya ndi kudula, kuwotcha, kapena matenda-LL-37 imatulutsidwa pamalo ovulala, kumene imalimbikitsa kusamuka ndi kufalikira kwa maselo a epithelial (maselo omwe amayendetsa pamwamba pa thupi), kuthandiza kumanganso minofu yowonongeka (njira yotchedwa re-epithelialization). Zimalimbikitsanso angiogenesis-kupangidwa kwa mitsempha yatsopano ya magazi-yomwe ndi yofunika kwambiri popereka mpweya ndi zakudya kumalo owonongeka, kufulumizitsa kuchira.

Kafukufuku wasonyeza kuti milingo ya LL-37 imakwezedwa pakuchiritsa mabala, ndipo zofooka za LL-37 zimalumikizidwa ndi kuchedwa kuchira kwa mabala, monga mwa anthu omwe ali ndi matenda a shuga kapena zilonda zam'mimba. Polimbikitsa kukula kwa maselo a epithelial ndi mapangidwe a mitsempha ya magazi, LL-37 imathandizira kubwezeretsa umphumphu wa minofu ndikuletsa matenda kuti asagwire malo owonongeka.

Antitumor Effects: Chida Chokhoza Kulimbana ndi Khansa

M’zaka zaposachedwapa, ofufuza atulukira zimeneziLL-37ilinso ndi antitumor properties, zomwe zimapangitsa kuti ikhale chandamale chothandizira chithandizo cha khansa. Zimagwira ntchito m'njira zingapo zolimbana ndi khansa: choyamba, imapangitsa apoptosis (kufa kwa maselo a khansa) m'maselo a khansa, kuwalepheretsa kuchulukitsa ndi kufalikira. Chachiwiri, amalepheretsa chotupa angiogenesis, kudula magazi kuti zotupa ayenera kukula ndi metastasize (kufalikira ku mbali zina za thupi). Chachitatu, imathandizira chitetezo chamthupi, kuthandiza chitetezo chamthupi kuzindikira ndikuukira maselo a khansa, omwe nthawi zambiri amatha kupeŵa kuzindikiridwa ndi chitetezo chamthupi.

Kafukufuku wasonyeza zimenezoLL-37imasonyezedwa m’mitundu yosiyanasiyana ya khansa, kuphatikizapo khansa ya m’mawere, khansa ya m’mapapo, ndi khansa yapakhungu, ndipo milingo yake nthawi zambiri imayendera limodzi ndi zotsatirapo za odwala. Mwachitsanzo, milingo yapamwamba ya LL-37 m'makhansa ena imalumikizidwa ndi kupulumuka bwino, chifukwa imathandizira kupondereza kukula kwa chotupa (Zhang C, et al., 2022). Kuphunzira kwathunthu pa zotsatira za antitumor za LL-37 zitha kupezeka apa: https://doi.org/10.1016/j.celrep.2022.111005.

LL-37 mu Clinical Practice: Zotsatira za Matenda ndi Chithandizo

Chifukwa cha ntchito zake zambiri, LL-37 ili ndi zofunikira pazachipatala. Miyezo yachilendo ya LL-37-kaya kusowa kapena kupitirira-kumagwirizana ndi matenda osiyanasiyana. Mwachitsanzo, kusowa kwa LL-37 kumayenderana ndi matenda obwera mobwerezabwereza (popeza chitetezo chakutsogolo cha thupi chimakhala chofooka), atopic dermatitis (matenda otupa akhungu), rosacea, ndi matenda osachiritsika a m'mapapo (COPD). Kumbali ina, kuchuluka kwa LL-37 kumalumikizidwa ndi zovuta za autoimmune komanso zotupa monga psoriasis, lupus, ndi nyamakazi ya nyamakazi, pomwe chitetezo chamthupi chimakhala chochulukirapo.

Mayanjano awa apangaLL-37cholinga chodalirika cha chitukuko chamankhwala. Mwachitsanzo, ma peptides opangidwa a LL-37 akuphunziridwa ngati njira zina zochotsera maantibayotiki, makamaka popeza kukana kwa maantibayotiki kukukulirakulira padziko lonse lapansi. Akufufuzidwanso kuti agwiritsidwe ntchito posamalira mabala kuti afulumire kuchira komanso kupewa matenda. Kuphatikiza apo, mankhwala opangira LL-37 akufufuzidwa pochiza khansa, matenda a autoimmune, ndi matenda otupa (Deslouches B, et al., 2017). Dziwani zambiri za kuthekera kwachire kwa LL-37 apa: https://doi.org/10.1128/AAC.02377-16.

Zofunika Kwambiri: Chifukwa Chake LL-37 Imafunika

LL-37Ndi chinthu chochulukirapo kuposa peptide ya antimicrobial - ndi molekyulu yogwira ntchito zambiri yomwe imakhala pamzere wa chitetezo chamthupi, kuwongolera matenda, kukonza minofu, ndi kuwongolera matenda. Mapangidwe ake apadera amalola kulimbana ndi tizilombo toyambitsa matenda osiyanasiyana, kulimbitsa chitetezo cha mthupi, kuchiritsa minyewa yowonongeka, komanso kuthana ndi khansa. Pomwe kafukufuku akupitilira kuwulula kuthekera kwake konse, LL-37 yatsala pang'ono kukhala chida chofunikira polimbana ndi kukana maantibayotiki, kutupa kosatha, ndi khansa.

Kaya ndinu wofufuza, wothandizira zaumoyo, kapena mukungofuna kudziwa momwe chitetezo chanu cha mthupi chimagwirira ntchito, LL-37 ndi molekyulu yofunikira kudziwa. Kusinthasintha kwake komanso kufunikira kwachipatala kumapangitsa kuti ikhale imodzi mwamagawo osangalatsa kwambiri pa kafukufuku wa immunology masiku ano.