title: Extracellular matrix from porcine small intestinal submucosa (SIS) as immune adjuvants.
abstract: Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and hapten-protein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate-keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomes-related genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of chemotactic factors LIX and KC (neutrophil chemotactic factors), MCP-1 (monocytes chemotactic factors), MIP 1-α (macrophage chemotactic factor) and lymphotactin, as well as, growth factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specific antibody response, primarily of IgG1 type.
authors.affiliation: Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Aachoui
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ghosh
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology*; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018925:Chemokines / Q000032:analysis / Q000235:genetics; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005109:Extracellular Matrix / Q000276:immunology / Q000637:transplantation*; D020869:Gene Expression Profiling; D007249:Inflammation; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D007421:Intestine, Small / Q000166:cytology; D051379:Mice; D023421:Models, Animal; D013552:Swine; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D018925:Chemokines; D016207:Cytokines; D014612:Vaccines; C041524:aluminum sulfate
references.citation: J Immune Based Ther Vaccines. 2006 Oct 30;4:6
references.pmid: 17074094
references.citation: Immunology. 2002 Jun;106(2):222-8
references.pmid: 12047751
references.citation: Stem Cells. 1994;12 Suppl 1:15-24; discussion 25
references.pmid: 7696959
references.citation: Clin Orthop Relat Res. 1999 Oct;(367 Suppl):S333-43
references.pmid: 10546657
references.citation: J Immunol. 2008 Sep 15;181(6):3755-9
references.pmid: 18768827
references.citation: Tissue Eng. 1996 Fall;2(3):209-17
references.pmid: 19877943
references.citation: Nat Immunol. 2010 Feb;11(2):136-40
references.pmid: 20023662
references.citation: Biochim Biophys Acta. 2004 Mar 4;1654(1):13-22
references.pmid: 14984764
references.citation: World J Urol. 2000 Feb;18(1):26-30
references.pmid: 10766040
references.citation: J Leukoc Biol. 2008 Apr;83(4):817-21
references.pmid: 18192490
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2927-32
references.pmid: 21270336
references.citation: Acta Biomater. 2010 Jun;6(6):2091-6
references.pmid: 19887120
references.citation: Tissue Eng. 2002 Feb;8(1):53-62
references.pmid: 11886654
references.citation: Arthritis Res Ther. 2008;10(6):228
references.pmid: 19090963
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10501-6
references.pmid: 18650390
references.citation: Immunology. 2003 Dec;110(4):482-92
references.pmid: 14632646
references.citation: J Immunol. 1984 Sep;133(3):1677-82
references.pmid: 6205092
references.citation: J Cell Biochem. 1997 Dec 15;67(4):478-91
references.pmid: 9383707
references.citation: Anticancer Res. 2008 Sep-Oct;28(5A):2529-34
references.pmid: 19035274
references.citation: J Exp Med. 2008 Apr 14;205(4):869-82
references.pmid: 18362170
references.citation: Cancer Immunol Immunother. 2007 Aug;56(8):1275-83
references.pmid: 17242926
references.citation: Surg Innov. 2005 Sep;12(3):227-31
references.pmid: 16224643
references.citation: J Surg Res. 2002 Apr;103(2):190-202
references.pmid: 11922734
references.citation: Annu Rev Immunol. 1994;12:991-1045
references.pmid: 8011301
references.citation: Curr Opin Cell Biol. 2002 Oct;14(5):608-16
references.pmid: 12231357
references.citation: Eur J Immunol. 2008 Mar;38(3):750-62
references.pmid: 18236400
references.citation: J Cell Sci. 2008 Feb 1;121(Pt 3):255-64
references.pmid: 18216330
references.citation: Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1-13
references.pmid: 2700931
references.citation: Curr Opin Immunol. 2009 Feb;21(1):23-9
references.pmid: 19246182
references.citation: Cell Immunol. 2011;271(2):227-38
references.pmid: 21813116
references.citation: Nat Rev Immunol. 2010 Mar;10(3):210-5
references.pmid: 20168318
references.citation: J Leukoc Biol. 2001 Dec;70(6):849-60
references.pmid: 11739546
references.citation: Crit Rev Immunol. 1999;19(2):155-72
references.pmid: 10352902
references.citation: Urology. 1995 Sep;46(3):396-400
references.pmid: 7660517
references.citation: J Neurosurg. 2007 Jun;106(6):1028-33
references.pmid: 17564175
references.citation: Science. 1985 Jul 5;229(4708):16-22
references.pmid: 2990035
references.citation: Transplantation. 2001 Jun 15;71(11):1631-40
references.pmid: 11435976
references.citation: Immunology. 2006 Jun;118(2):143-52
references.pmid: 16771849
references.citation: Biomed Pharmacother. 2004 Jun;58(5):325-37
references.pmid: 15194169
references.citation: Curr Opin Immunol. 2007 Dec;19(6):615-22
references.pmid: 17977705
references.citation: Vaccine. 2011 Mar 16;29(13):2461-73
references.pmid: 21256188