title: Calcium-binding protein, spermatid-specific 1 is expressed in human salivary glands and contains an anti-inflammatory motif.
abstract: Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined.
authors: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and.
authors: Chris D
authors: CD
authors: St Laurent
authors: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and.
authors: Katherine E
authors: KE
authors: St Laurent
authors: Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Ron D
authors: RD
authors: Mathison
authors: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and dean.befus@ualberta.ca.
authors: A Dean
authors: AD
authors: Befus
mesh_terms: D020816:Amino Acid Motifs; D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012469:Salivary Glands / Q000378:metabolism*; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; C000598353:CABS1 protein, human; D002135:Calcium-Binding Proteins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D012471:Salivary Proteins and Peptides; C066861:Smr3b protein, rat; C482199:lipopolysaccharide, E coli O55-B5; D010047:Ovalbumin
keywords: SMR1; Vcsa1; inflammation; neutrophilia; saliva
references: Neuroscience. 2006 Jul 7;140(3):1011-22
references: 16581192
references: Horm Behav. 2004 Dec;46(5):684-91
references: 15555512
references: Neuroreport. 2006 Nov 27;17(17):1793-6
references: 17164666
references: BJU Int. 2007 Feb;99(2):431-5
references: 17026587
references: J Urol. 2007 Jul;178(1):338-43
references: 17512016
references: Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G1094-9
references: 18308855
references: J Proteome Res. 2008 May;7(5):1994-2006
references: 18361515
references: BJU Int. 2008 Sep;102(6):736-40
references: 18410445
references: Recent Pat Inflamm Allergy Drug Discov. 2007 Jun;1(2):124-32
references: 19075974
references: Am J Physiol Cell Physiol. 2009 Mar;296(3):C514-24
references: 19109528
references: Biol Reprod. 2009 Jun;80(6):1293-304
references: 19208547
references: J Proteome Res. 2009 Jun;8(6):2953-65
references: 19271754
references: Inflamm Res. 2009 Aug;58(8):457-62
references: 19255722
references: Peptides. 2000 Mar;21(3):443-55
references: 10793230
references: Eur J Pharmacol. 2000 Dec 8;409(2):203-5
references: 11104835
references: Proc West Pharmacol Soc. 2001;44:157-8
references: 11793968
references: Peptides. 2002 Jan;23(1):193-9
references: 11814634
references: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8549-54
references: 12835417
references: Genomics. 2003 Oct;82(4):417-32
references: 13679022
references: BMC Immunol. 2003 Mar 4;4:3
references: 12659660
references: J Proteome Res. 2009 Dec;8(12):5590-600
references: 19813771
references: Eur J Immunol. 2004 Dec;34(12):3315-25
references: 15549777
references: Vet Immunol Immunopathol. 2009 Dec 15;132(2-4):175-80
references: 19577809
references: Peptides. 2003 Aug;24(8):1221-30
references: 14612194
references: Peptides. 2010 Jun;31(6):1076-82
references: 20214943
references: J Clin Invest. 2011 Apr;121(4):1484-96
references: 21436586
references: Pulm Pharmacol Ther. 2013 Apr;26(2):167-71
references: 23041650
references: Chest. 2013 Feb 1;143(2):371-8
references: 22846981
references: J Histochem Cytochem. 1993 Nov;41(11):1645-9
references: 8409372
references: Eur J Biochem. 1994 Feb 1;219(3):765-73
references: 8112327
references: Am J Physiol. 1997 Sep;273(3 Pt 2):R1017-23
references: 9321881
references: Dig Dis Sci. 1997 Nov;42(11):2378-83
references: 9398820
references: Peptides. 1998;19(6):1037-42
references: 9700752
references: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17979-84
references: 17101991