title: Anti-inflammatory actions of serine protease inhibitors containing the Kunitz domain.
abstract: BACKGROUND
  Protease inhibitors, including the Kunitz, Kazal, serpin and mucus families, play important roles in inhibiting protease activities during homeostasis, inflammation, tissue injury, and cancer progression. Interestingly, in addition to their anti-protease activity, protease inhibitors also often possess other intrinsic properties that contribute to termination of the inflammatory process, including modulation of cytokine expression, signal transduction and tissue remodeling. In this review we have tried to summarize recent findings on the Kunitz family of serine proteinase inhibitors and their implications in health and disease.
  
  
  METHODS
  A systematic search was performed in the electronic databases PubMed and ScienceDirect up to October 2009. We tried to limit the review to anti-inflammatory actions and actions not related to protease inhibition.
  
  
  CONCLUSIONS
  Recent studies have demonstrated that the Kunitz inhibitors are not only protease inhibitors, but can also prevent inflammation and tissue injury and subsequently promote tissue remodeling.
authors.affiliation: Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shigetomi
authors.forename: Akira
authors.initials: A
authors.lastname: Onogi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kajiwara
authors.forename: Shozo
authors.initials: S
authors.lastname: Yoshida
authors.forename: Naoto
authors.initials: N
authors.lastname: Furukawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Haruta
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanase
authors.forename: Seiji
authors.initials: S
authors.lastname: Kanayama
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Oi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D015842:Serine Proteinase Inhibitors
references.citation: J Surg Res. 2000 Dec;94(2):107-15
references.pmid: 11104650
references.citation: Crit Care Med. 2002 Mar;30(3):617-22
references.pmid: 11990925
references.citation: J Biol Chem. 2009 Jun 19;284(25):16922-16930
references.pmid: 19395377
references.citation: Nature. 1964 Jul 18;203:255-7
references.pmid: 14201757
references.citation: Biomed Pharmacother. 2003 Sep;57(7):269-73
references.pmid: 14499171
references.citation: J Infect Dis. 2005 Mar 15;191(6):930-8
references.pmid: 15717269
references.citation: Biochim Biophys Acta. 2000 Sep 29;1481(2):310-6
references.pmid: 11018722
references.citation: Crit Care Med. 2004 Aug;32(8):1747-52
references.pmid: 15286553
references.citation: Am J Respir Cell Mol Biol. 2007 Jan;36(1):20-31
references.pmid: 16873769
references.citation: J Infect Dis. 2000 Mar;181(3):1101-9
references.pmid: 10720537
references.citation: J Biol Chem. 2005 Jul 29;280(30):27832-8
references.pmid: 15932872
references.citation: J Pathol. 2006 Feb;208(3):327-39
references.pmid: 16261634
references.citation: J Mol Biol. 1999 Nov 26;294(2):587-99
references.pmid: 10610782
references.citation: Shock. 2001 Feb;15(2):101-5
references.pmid: 11220636
references.citation: Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):233-42
references.pmid: 17951326
references.citation: Int J Cancer. 2006 May 1;118(9):2322-8
references.pmid: 16331631
references.citation: Expert Opin Drug Saf. 2008 Nov;7(6):663-77
references.pmid: 18983214
references.citation: Cell Mol Life Sci. 2003 Mar;60(3):463-73
references.pmid: 12737307
references.citation: J Biol Chem. 2006 Jun 30;281(26):17827-37
references.pmid: 16641089
references.citation: Arterioscler Thromb Vasc Biol. 2002 Apr 1;22(4):539-48
references.pmid: 11950688
references.citation: J Biol Chem. 2003 Apr 25;278(17):14640-6
references.pmid: 12571229
references.citation: J Biol Chem. 2009 Jul 24;284(30):20136-46
references.pmid: 19491101
references.citation: Biochim Biophys Acta. 1998 Jul 23;1381(2):139-46
references.pmid: 9685617
references.citation: Am J Pathol. 2009 Jun;174(6):1993-5
references.pmid: 19435789
references.citation: Oncogene. 2007 Mar 8;26(11):1546-56
references.pmid: 16983341
references.citation: Saudi Med J. 2008 Mar;29(3):368-73
references.pmid: 18327361
references.citation: Hepatol Res. 2004 Aug;29(4):243-248
references.pmid: 15288018
references.citation: FEBS Lett. 2006 Jan 9;580(1):245-50
references.pmid: 16364318
references.citation: Thromb Haemost. 2005 Dec;94(6):1122-30
references.pmid: 16411383
references.citation: Inflammation. 1991 Feb;15(1):71-9
references.pmid: 1711513
references.citation: Curr Protein Pept Sci. 2003 Jun;4(3):231-51
references.pmid: 12769721
references.citation: Orthopedics. 2004 Jun;27(6 Suppl):s659-62
references.pmid: 15239553
references.citation: Biol Chem Hoppe Seyler. 1994 Aug;375(8):521-6
references.pmid: 7529027
references.citation: J Biol Chem. 1994 Nov 11;269(45):28282-7
references.pmid: 7525572
references.citation: Crit Rev Eukaryot Gene Expr. 1995;5(3-4):385-436
references.pmid: 8834232
references.citation: Ann N Y Acad Sci. 2007 Jan;1096:86-8
references.pmid: 17405919
references.citation: Biol Chem. 2003 May;384(5):749-54
references.pmid: 12817471
references.citation: Semin Thromb Hemost. 2003 Apr;29(2):175-84
references.pmid: 12709921
references.citation: BMC Mol Biol. 2007 Dec 03;8:110
references.pmid: 18053161
references.citation: J Biol Chem. 2005 Jul 8;280(27):25674-86
references.pmid: 15840581
references.citation: Hum Cell. 2009 Feb;22(1):11-7
references.pmid: 19222607
references.citation: J Biol Chem. 2002 Apr 19;277(16):14053-9
references.pmid: 11805118
references.citation: Folia Microbiol (Praha). 2007;52(2):159-73
references.pmid: 17575915
references.citation: Arthritis Res Ther. 2003;5(4):R186-92
references.pmid: 12823853
references.citation: World J Gastroenterol. 2005 Mar 21;11(11):1605-9
references.pmid: 15786535
references.citation: J Biochem. 1996 Aug;120(2):271-5
references.pmid: 8889810
references.citation: Biochem Soc Trans. 2006 Jun;34(Pt 3):446-50
references.pmid: 16709183
references.citation: Semin Cardiothorac Vasc Anesth. 2006 Jun;10(2):132-42
references.pmid: 16959740
references.citation: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1265-71
references.pmid: 15539418
references.citation: Thromb Haemost. 2005 Jul;94(1):136-45
references.pmid: 16113797
references.citation: Pharmacotherapy. 2008 Jan;28(1):112-24
references.pmid: 18154481
references.citation: Biochim Biophys Acta. 2001 May 28;1519(1-2):92-5
references.pmid: 11406276
references.citation: J Biol Chem. 2003 Sep 19;278(38):36341-9
references.pmid: 12815039
references.citation: Osteoarthritis Cartilage. 2008 Nov;16(11):1343-55
references.pmid: 18524635
references.citation: Curr Top Dev Biol. 2007;78:23-46
references.pmid: 17338914
references.citation: J Endotoxin Res. 2007;13(6):369-76
references.pmid: 18182464
references.citation: Apoptosis. 2007 Dec;12(12):2163-73
references.pmid: 17885802
references.citation: Adv Clin Chem. 2007;44:223-45
references.pmid: 17682344
references.citation: Gynecol Obstet Invest. 1996;41(2):96-102
references.pmid: 8838968
references.citation: J Biol Chem. 2007 Oct 12;282(41):30161-70
references.pmid: 17675295
references.citation: Hepatobiliary Pancreat Dis Int. 2009 Feb;8(1):53-8
references.pmid: 19208516
references.citation: Int J Biochem Cell Biol. 2000 Feb;32(2):125-37
references.pmid: 10687949
references.citation: Biochem J. 1996 Apr 1;315 ( Pt 1):1-9
references.pmid: 8670091
references.citation: Am J Pathol. 2009 Apr;174(4):1309-18
references.pmid: 19286566
references.citation: Cancer Res. 2005 Jun 1;65(11):4598-606
references.pmid: 15930277
references.citation: Annu Rev Cell Dev Biol. 2007;23:435-61
references.pmid: 17506690
references.citation: Anticancer Res. 2008 Jul-Aug;28(4A):1977-83
references.pmid: 18649735
references.citation: Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):310-6
references.pmid: 17138934
references.citation: J Immunol. 1993 Mar 1;150(5):1804-12
references.pmid: 7679696
references.citation: Biochemistry. 1972 Aug 1;11(16):2967-77
references.pmid: 5041905
references.citation: Adv Exp Med Biol. 2009;653:98-116
references.pmid: 19799114
references.citation: Drug News Perspect. 2008 Sep;21(7):369-81
references.pmid: 19259550
references.citation: Arch Biochem Biophys. 1999 Oct 1;370(1):112-8
references.pmid: 10496984
references.citation: Int J Cancer. 2006 Sep 1;119(5):1176-83
references.pmid: 16557597
references.citation: J Biol Chem. 1997 Mar 7;272(10):6370-6
references.pmid: 9045658
references.citation: Clin Chim Acta. 1980 Nov 6;107(3):211-5
references.pmid: 7438456
references.citation: Hoppe Seylers Z Physiol Chem. 1981 Oct;362(10):1351-5
references.pmid: 6171496
references.citation: Exp Biol Med (Maywood). 2005 Apr;230(4):281-7
references.pmid: 15792950
references.citation: BMC Cancer. 2008 Jan 28;8:25
references.pmid: 18226209
references.citation: J Biol Chem. 2004 Sep 10;279(37):38079-82
references.pmid: 15151994
references.citation: J Biol Chem. 1990 Mar 25;265(9):5247-57
references.pmid: 1690737
references.citation: J Am Soc Nephrol. 2006 Jun;17(6):1553-67
references.pmid: 16687630
references.citation: J Biol Chem. 2002 Dec 27;277(52):51068-76
references.pmid: 12401803
references.citation: FEBS Lett. 1997 Nov 17;417(3):337-40
references.pmid: 9409746