Asadi, Arash

Simorgh Research Repository

"1/4/"fu",rS,.},,;1 olS,i,ll.l,$-X ,-l'..1. JS.:I r,^.-il g;iS, :LU <-l: ;Lt1:;13',cq AlfX c,-3li- ;.r (;1 ,:...1':(J L^ Ji*.j+. t+)d.r-SJ- .r,: 6La ,::i* gF31.$L".l.at .f,rll. JJ1S Y\ i*5:J, csJ$).rJ-r,.r"*l ..!6o -,siL t..t .+'..t cniisBALBic cSLa "F*r;.1 ..,*,,,lLq q,o.d -.ir,:-oi f-r,t+l6;-l cF;I : L...,:,r;;lt ,.^^ liS.l :L"i^l-r ll':,"1. J. >.i - ,rl iS., : ,rl.+.o .ll:...1(J -r (:v- Y\Ylo -\Y11 :.J:,--: Jl-.l:t:,:."gKerman University of Medical SciencesFaculfy of MedicineIn Partial Fulflllment of the Requirements for PhD Degree in MedicalParasitologyTitle:The Role of Antimicrobial Peptides @eta Defensins & Cathelicidin) in HostResistance to Leishmania major Infection and Immonomodulatory Activity' of Protein 21 KDa of Gentamicin Attenuated Leishmania InfantuminBALB/c MiceBy: Arash AsadiSupervisor: Dr. Hamid DaneshvarAdvisor: Dr. Iraj SharifiYear: 2017-2018( Q+r*"e;l',"p,t/;o_w*r'ly" ,Slfi r; .sG{*. .r;lr orq-r ,e Ut*l J<l +b ,jl.ai- tl.!r ,r) cso&. .ijij (Jjl, .r:--l :a,o.r-,r"t.t & .c-l o-r; c,-),p p+l{d.sl},,j/.!. ) sn o& rtnai ,rcl-ir dn aJ -r:.^a p-ao;-l ;l j-:,*i-LsE- ,:-i rt,;y. L aJlt J9l -!ro.):-.r;iL- q"j;. lrl .rJ c,Ult ,.rJ+.jl*L.,;*l 5)s" .::.ty'I. iJ Y\ J"jj'9), S;i\ gbyt"t.l .JUi ,;i 2 o9Vu- )y r)G lrl^.rrJ ..1' gGr -2r g9f- r- .51-o-.4.tF ,_t,;y d ,_,1_t I ctgtr 66 Jr.;l 6--LLa L o,r";, q=";l frxl-oj,-l l!'*-! ljt l*l--.J ;fo + (C51BL|6) rs6 t (BALB/c) ,.*L- .sl+,;r e tbjl.let't :Lb 9i92 9 :l,re)t9, .gG a'9* ,u!>9)i )l u-" )s-) c.ab 9 4r ,&- .r,;u +ls" $L lrl*,iJ Js.;l -li Sr .sL^ c-95*;1".--.r*;9 \Y i \. .rll O$l*.5,]-{,-15 ,\f ,2 ,,F.Y,Y,\ .51,o e.*;-0,-r bmRNA ;rly ";'>'-- cSlx;=,J Y\ Usst s)S s*V ,tlx: a,.;3..l .r;u ,;-U;'i L-^5 s:r"i.(;, e qPCR csLo .ji1 L e j;l .,i:.,] ,-t9i 9 o9l r)9e BALB/c .rQjr ,-;-l ,'--.,- 69t t ofi cK;;l;.rl"lr-;l orj ,a^lx, ,r,;:.-l-r,f __*JS:l 1r .:lr ,:1, ;;9;,s- c,r"; 1l ,b ,r;" ";olt .i- BALB/c cSb .lr ;l o-r; ";;- .gl,ojG9y't :p-L;r; .SL+^* fl; Olr: e+- 4? ,51 .srb ;[u.: C57BL|6 ;l o;; j'r.;-. .5tojGerst ! a*-lc" ,,) !f-+1jll ,,"f ;l oL; 6;; .5to;Grrit ! o*-G" ,,, Jil L o-rj a-19. BALB/c .5U .J",. i e:,3=.r-r,5 e+ , (- ;*-:o,-r l+ L,,-+*tt ,Slt &;lr d,* 7lL- ag9;-l L ,1r9, a;it- Lri-lt'l C57BL nqi o-r,-ij -bu.;l .5ta OU; Fl1r .5;lr ,-r* t* a, BALB/c 6l.o u"f 1r o-r,i 2l! ,_sl,  j nl- .,,! e,*-t*r i .r-+*J:l .sb Oj ,:V. e*- 6b G* ,* + .;llt rJ Y\ o*e-t, .;;b ,i-l;il ,1e; +f -,t*,* *.:isx;,-l ;,::-o.:f 'Ul BALB/c.rh "pr 1l ou 4;;.5to;l-igriL r:1., \f ;=--;-:.rl': ,i-l;-ilBALB/c dta .r"r ,r l1 Llf Jtf /4.1.,1* tl*;tC )"; 6-Ldtl IgG +Jr 1l: ;--, ;.g[ltsrft 9 BALB/c .gl' ,:"t" i Ge;* r;.rGr+" eb- c"9, rY!,"r,, .)s:r5y! aa;eC57BL|6 dU d"r. ,l r;*lr Jll ou l4i .rrjL Ul^;J L o.u oreJi BALB/c .sLo;e. 11 .-r; .JGr*;.1 oJ ,9^; ,r" 6.# a:.;; V[ cJlt ,il .r]rlr ;L;i C57BL|6 dll .,.f ;l o-r"; j;u ,gta,l!",J -:or$-'Ni\;/-:) t5aJtL. 3*7^,o .$9,- .r^j ,-:ilt i l^ib.. 4. )Zl-) JS t?, Lr" ,ll* Gf a.. t J(.il 41t 3Gl ,S1l G.t:(-.r-L".5lrsil sl9;.j" ax,--th+ L ou .-o-*"r'pfll:.l LLJ ;y'lrr*t Y\ ,-tilx al .:1.: ;L;; --.59; #.f F ,,) b .-i, 1r StL" G+l ; .-.tll, /J Y\ Jirj, .rriL ULJ ,, ,uis, ux*.rr,-: ! ,U-+-15 , G9f* -r- .gG.:"; :6q15 CitJitf ;J9lr-_l ,\. OJ!;"-l ,d,:--Lt+ L o.r; , i*^: p9::1;;,-l L;i^--{bstractIntroduction: Innate immunity has an important role against leisltmania parasite.\ntimicrobial peptides (AMPs) are proteins of this systern that their defense roles have beennvestigated verslls some invasive pathogens. Despite uumerolls cases of cutaneousleishrnaniasis, few studies are found at this background. The first aim of our study was toinvestigate about AMPs protective role against L. ntajor. Additionally. the immnomodulatoryactivity of protein 2l KDa of Gentamicin attenuated L. infanturu was investigated in both irlllo and in yitro rnodels.Material and Methods: Macrophages, susceptible (BALB/c) and resistant (C5lBLl6) rnousestrains were exposed with the stationary phase of L. major promastigotes. After 1, 3 and 7days of post infection (PI). tlie samples needed for detecting of rnRNA levels of mouse betadefensin (mBD)-1. mBD2. mBD3. mBD4, rnBD6, cathljn-related antimicrobial peptide(CRAMP). interleukin (lL)-10, IL-12 and parasite load were taken and analyzed Lrsing qPCRartd Giemsa methods. Also, the effectiveness rate of 2l KDa protein purified from transfected cellsx'as determined on BALB/c nrice irnmunity system both in vivo and in vitro models.Result: C57BLl6 derived macrophages showed a significant reduction (p<0.05) of infectionseverity compared to BALB/c derived macrophages. Although the explession level of all{MPs in BALB/c derived macrophages challenged by parasite had been increased comparedto C57BL/6 derived macrophages, neveftheless. significant levels (p<0.05) documented onlyibr CRAMP and mBDl. The expression levels of all aforementioned genes in BALB/c miceincreased significantly (p<0 05) compared to other strain at mostly selected times. L. infantttmPl1 indLrced significantly (p<0.05) the expression levels of CRAMP and mBD14 genes inBALB/c derived macrophages. It also promoted significantly (p<0.05) the production ofspecrfic anti-leishmania IgC and IFN-y gene expression BALB/c mice.Conclusion: Despite of higher expression of AMPs in BALBic mice and BALB/c derivednracroplrages infected hy L. ruajor. they showed infection severity more than C57BL/6 rniceand C57BL/6 derived macrophages. It is concluded from the above statement that AMPsrenes are lvell expressed to provide defense against the parasites but cannot create an absolute:rotection. The present study also showed that P21 KDa Gentarnicin attenuated L. infbntum;an be considered as a good candidate in dog's inrnrunization.Kev rvords: Antimicrobial peptides, Cathelicidin. Defensin, Mouse B-defensin. lei,shnronict. -;i or'. 27 I(Da Gentamicin attunated leishruania iffintttnt, [L- 10, lL-12.,,19:rt4'!#a., ..,' }i,,,:. -............,...-.,..i,,i;.,-' ",.'..''..,,..;*,j,f#u e4*{{slj ,'.L1, i! .rli+ .r"*-l*,*aL\;i" #i1,$.: ,ir-!"",'$ ;j.r.-i: .:.*t,:.: .sur j;i ; riT.,a*- +ai ..... .,..- ,"-:i :.t.r ,t* r.*.-..; '' ,jji"-;.Lr;,--*1-..--.,**,!i.;j+:.rj.:,..,._;-ir.*i, ,:i: ir-,t,,... t* *tu jL,r _,,-.. -!,):1... .,,..:1:r--- .;,-.J. -i,t 1i i)r.\ ...."

The role of antimicrobial peptides ( Beta Defensins & Cathelicidin ) in host resistance to Leishmania major infection & immonomodulatory activity of protein 21 KDa of Gentamicin attenuated leishmania infantum in BALB/c Mice

http://eprints.kmu.ac.ir/27008/1/6443.pdf

The role of antimicrobial peptides ( Beta Defensins & Cathelicidin ) in host resistance to Leishmania major infection & immonomodulatory activity of protein 21 KDa of Gentamicin attenuated leishmania infantum in BALB/c Mice

Abstract

Similar works

Full text

Available Versions

Simorgh Research Repository