title: Oral administration of poly-γ-glutamate ameliorates atopic dermatitis in Nc/Nga mice by suppressing Th2-biased immune response and production of IL-17A.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is closely related to dysregulation of the T helper type 1 and 2 (Th1)/Th2 balance. A previous study showed that high molecular mass poly-γ-glutamate (γ-PGA) isolated from Bacillus subtilis sp. Chungkookjang induces the production of IL-12 from dendritic cells (DCs). Here, we investigated the effect of γ-PGA on AD-like skin disease using an Nc/Nga mouse model. In vitro, γ-PGA activated DCs and induced IL-12 production in mice. In vivo, oral administration of γ-PGA markedly reduced the AD symptoms, similar to the response seen in the dexamethasone (Dex)-treated group. Treatment with γ-PGA also decreased the serum levels of IgG1, the skin levels of Th2 cytokines, the extent of skin inflammation, and the accumulation of mast cells. Furthermore, γ-PGA was effective against established AD, significantly decreasing serum IgE and Th2 cytokines in the inflamed tissue. Interestingly, the production of IL-17A in splenocytes was also suppressed by γ-PGA, indicating that it inhibits both Th2 and Th17 immune responses. Collectively, these results suggest that oral administration of γ-PGA could be a therapeutic strategy for treating AD via the modulation of Th2-biased immune responses in an Nc/Nga mouse model.
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Doo-Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Ji-Na
authors.initials: JN
authors.lastname: Won
authors.affiliation: Bioleaders Corporation, Daejeon, Republic of Korea.
authors.forename: Il-Han
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Advanced Fermentation Fusion Science and Technology, Kookmin University, Seoul, Republic of Korea.
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea. Electronic address: haryoung@kribb.re.kr.
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D003879:Dermatologic Agents; C098680:Il17a protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; C511775:poly(gamma-glutamic acid); D018664:Interleukin-12; D011099:Polyglutamic Acid; D007073:Immunoglobulin E
references.citation: Crit Rev Biotechnol. 2007 Jan-Mar;27(1):1-19
references.pmid: 17364686
references.citation: J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S1-S12
references.pmid: 11145790
references.citation: J Immunol Methods. 1999 Feb 1;223(1):77-92
references.pmid: 10037236
references.citation: Int Rev Cytol. 1996;167:91-159
references.pmid: 8768493
references.citation: Jikken Dobutsu. 1973;22 Suppl(0):271-6
references.pmid: 4807756
references.citation: Int Arch Allergy Immunol. 1999;120 Suppl 1:70-5
references.pmid: 10529609
references.citation: Ann Allergy. 1992 Dec;69(6):469-79
references.pmid: 1471777
references.citation: Med J Aust. 1992 Mar 16;156(6):428-31
references.pmid: 1545752
references.citation: Nat Genet. 2006 Apr;38(4):441-6
references.pmid: 16550169
references.citation: Clin Vaccine Immunol. 2012 Jan;19(1):17-22
references.pmid: 22089248
references.citation: J Immunol. 2010 Mar 1;184(5):2729-35
references.pmid: 20107184
references.citation: J Allergy Clin Immunol. 2007 Jul;120(1):150-5
references.pmid: 17512043
references.citation: Chem Rec. 2005;5(6):352-66
references.pmid: 16278834
references.citation: Cancer Immunol Immunother. 2009 Nov;58(11):1781-94
references.pmid: 19294383
references.citation: J Biochem Mol Biol. 2007 Jul 31;40(4):486-93
references.pmid: 17669263
references.citation: J Clin Invest. 2005 Mar;115(3):688-94
references.pmid: 15696197
references.citation: J Immunol. 2007 Mar 1;178(5):2979-86
references.pmid: 17312143
references.citation: J Invest Dermatol. 2007 Apr;127(4):808-16
references.pmid: 17096020
references.citation: Am J Pathol. 2010 May;176(5):2385-93
references.pmid: 20304960
references.citation: Immunogenetics. 2001 Feb;53(1):15-21
references.pmid: 11261926
references.citation: J Hered. 1972 May-Jun;63(3):135-40
references.pmid: 4557539
references.citation: Adv Ther. 2003 May-Jun;20(3):129-37
references.pmid: 12956254
references.citation: J Immunol. 1999 Jan 15;162(2):1056-63
references.pmid: 9916733
references.citation: J Clin Invest. 1999 Apr;103(8):1103-11
references.pmid: 10207161
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3):485-93, 493.e1
references.pmid: 19665780
references.citation: Cell. 1996 Aug 9;86(3):345-8
references.pmid: 8756716
references.citation: J Drug Target. 1993;1(3):245-9
references.pmid: 8069566
references.citation: Mol Microbiol. 2006 Jun;60(5):1091-8
references.pmid: 16689787
references.citation: N Engl J Med. 1999 Dec 23;341(26):1966-73
references.pmid: 10607813
references.citation: J Am Acad Dermatol. 2001 Nov;45(5):736-43
references.pmid: 11606925
references.citation: Asian Pac J Allergy Immunol. 2011 Dec;29(4):357-60
references.pmid: 22299316
references.citation: Clin Dermatol. 2003 May-Jun;21(3):193-200
references.pmid: 12781437
references.citation: J Interferon Cytokine Res. 2001 Mar;21(3):147-55
references.pmid: 11331037
references.citation: J Allergy Clin Immunol. 2003 Apr;111(4):875-81
references.pmid: 12704372
references.citation: J Allergy Clin Immunol. 2013 Feb;131(2):280-91
references.pmid: 23374260
references.citation: J Invest Dermatol. 2008 Nov;128(11):2625-2630
references.pmid: 18432274
references.citation: Clin Exp Immunol. 1997 Jan;107 Suppl 1:25-30
references.pmid: 9020932
references.citation: Int Immunopharmacol. 2013 Feb;15(2):424-32
references.pmid: 23352844
references.citation: J Immunol. 2007 Jul 15;179(2):775-80
references.pmid: 17617566
references.citation: J Immunol. 2007 Jan 1;178(1):584-91
references.pmid: 17182599
references.citation: Int Immunol. 1997 Mar;9(3):461-6
references.pmid: 9088984
references.citation: J Dermatol Sci. 2004 Sep;35(3):187-97
references.pmid: 15381240
references.citation: Clin Dermatol. 1997 Sep-Oct;15(5):715-21
references.pmid: 9313970
references.citation: Naturwissenschaften. 2002 Jan;89(1):11-22
references.pmid: 12008968
references.citation: Vaccine. 1998 Mar;16(5):536-41
references.pmid: 9491509
references.citation: J Clin Invest. 1999 Oct;104(8):1097-105
references.pmid: 10525048
references.citation: Vaccine. 2001 Oct 12;20(1-2):208-17
references.pmid: 11567766
references.citation: J Biol Chem. 2001 Jan 26;276(4):2313-6
references.pmid: 11096121
references.citation: J Clin Invest. 1994 Aug;94(2):870-6
references.pmid: 8040343