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DEFB4A  -  defensin, beta 4A

Homo sapiens

Synonyms: BD-2, DEFB-2, DEFB102, DEFB2, DEFB4, ...
 
 
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Disease relevance of DEFB4

 

Psychiatry related information on DEFB4

  • The expression of HBD-2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints [6].
 

High impact information on DEFB4

  • A cDNA for hBD-2 was identified by homology to hBD-1. hBD-2 is expressed diffusely throughout epithelia of many organs, including the lung, where it is found in the surface epithelia and serous cells of the submucosal glands [7].
  • Some members of the Ets family, Ets-1 and Ets-2, cooperate in transcription with the AP-1 transcription factor, the product of the proto-oncogene families, fos and jun, while others, Elk-1 and SAP-1, form ternary complexes with the serum response factor (SRF) [8].
  • Retinal cells also attach to a substratum of HBD-2 peptide, but fail to bind to a control peptide containing a scrambled amino acid sequence of HBD-2 [9].
  • The HBD-2 peptide also inhibits retinal cell adhesion to N-CAM, demonstrating the physiological importance of the amino acid sequence encoded by the HBD peptide [9].
  • We showed that healthy individuals, as well as patients with ulcerative colitis, have a median of 4 (range 2-10) HBD-2 gene copies per genome [10].
 

Chemical compound and disease context of DEFB4

 

Biological context of DEFB4

 

Anatomical context of DEFB4

  • The results indicate that commensal and pathogenic bacteria utilize different pathways in hBD-2 induction and suggest that epithelial cells from different body sites have common signaling mechanisms to distinguish between commensal and pathogenic bacteria [3].
  • However, in addition, hBD-2 induction by pathogenic bacteria in both oral and foreskin keratinocytes was blocked by inhibitors of NF-kappaB [3].
  • In view of the morphology of the LL-37-positive and hBD-2-positive mucosal lymphocytes, they are probably also B-cells [20].
  • Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium of patients with hepatolithiasis [21].
  • Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1beta or tumor necrosis factor-alpha [21].
 

Associations of DEFB4 with chemical compounds

  • HBD-2 mRNA expression was developmentally regulated, induced by the proinflammatory factor IL-1beta, and decreased by dexamethasone [18].
  • HBD3 bound both gB and heparan sulfate, but hBD1 and hBD2 bound neither [22].
  • Anti-integrin alpha(5)beta(1), antifibronectin, genistein, and PP2 suppress the Omp100-induced expression of hBD2, suggesting that Src kinase is involved through integrin alpha(5)beta(1) [23].
  • These results show the selective regulation of hBD-2-encoding gene in an organotypic epidermal model, in response to LPS [24].
  • Expression of NOD2 was detected in primary keratinocytes, and stimulation of these cells with MDP induced hBD-2 peptide release [11].
 

Physical interactions of DEFB4

 

Regulatory relationships of DEFB4

  • Further, neutralizing antibody against TNF-alpha or IL-8 partially inhibits the induction of hBD2 on bacterial contact [23].
  • HBD-1 presented the highest and most heterogeneous expression at the basal level (non-stimulated) as compared to expression of HBD-2 and HBD-3, which was significantly lower and homogeneous [27].
  • The treatment of HUCL cells with TLR2 neutralizing antibody resulted in a significant decrease in Pam3Cys-induced hBD2 production as well as IL-6, IL-8, and TNF-alpha secretion [5].
  • An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction [28].
  • Omp100 binds to fibronectin, an extracellular matrix inducing hBD2 via the MAP kinase pathway [23].
 

Other interactions of DEFB4

  • Subsequently, the NMR solution structures of HBD1 and HBD3 were determined using standard homonuclear techniques and compared with the previously determined solution structure of HBD2 [29].
  • We conclude that the activation of NF-kappaB (p50-p65) and AP-1 are crucial events for induction of hBD-2 in keratinocytes upon IL-1beta and PA stimulation [2].
  • The goal of this study is to investigate whether TLR2 mediates hBD2 induction through NF-kappaB in response to bacterial components in the human airway epithelia [30].
  • The use of an IL-1 receptor antagonist revealed that PA-mediated induction of hBD-2 is not dependent on IL-1 [2].
  • The Pam3Cys-induced hBD2 expression was completely blocked by NF-kappaB inhibitors and partially inhibited by p38 MAP kinase and the JNK inhibitors [5].
 

Analytical, diagnostic and therapeutic context of DEFB4

 

 

 

References

  1. Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. Hollox, E.J., Armour, J.A., Barber, J.C. Am. J. Hum. Genet. (2003) [Pubmed]
  2. Pseudomonas aeruginosa- and IL-1beta-mediated induction of human beta-defensin-2 in keratinocytes is controlled by NF-kappaB and AP-1. Wehkamp, K., Schwichtenberg, L., Schröder, J.M., Harder, J. J. Invest. Dermatol. (2006) [Pubmed]
  3. Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Chung, W.O., Dale, B.A. Infect. Immun. (2004) [Pubmed]
  4. Human beta-defensin-3 induction in H pylori-infected gastric mucosal tissues. Kawauchi, K., Yagihashi, A., Tsuji, N., Uehara, N., Furuya, D., Kobayashi, D., Watanabe, N. World J. Gastroenterol. (2006) [Pubmed]
  5. Toll-like receptor 2-mediated expression of beta-defensin-2 in human corneal epithelial cells. Kumar, A., Zhang, J., Yu, F.S. Microbes Infect. (2006) [Pubmed]
  6. Production of endogenous antibiotics in articular cartilage. Varoga, D., Pufe, T., Harder, J., Meyer-Hoffert, U., Mentlein, R., Schröder, J.M., Petersen, W.J., Tillmann, B.N., Proksch, E., Goldring, M.B., Paulsen, F.P. Arthritis Rheum. (2004) [Pubmed]
  7. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. Bals, R., Wang, X., Wu, Z., Freeman, T., Bafna, V., Zasloff, M., Wilson, J.M. J. Clin. Invest. (1998) [Pubmed]
  8. The ets gene family. Macleod, K., Leprince, D., Stehelin, D. Trends Biochem. Sci. (1992) [Pubmed]
  9. Identification of a heparin binding domain of the neural cell adhesion molecule N-CAM using synthetic peptides. Cole, G.J., Akeson, R. Neuron (1989) [Pubmed]
  10. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Fellermann, K., Stange, D.E., Schaeffeler, E., Schmalzl, H., Wehkamp, J., Bevins, C.L., Reinisch, W., Teml, A., Schwab, M., Lichter, P., Radlwimmer, B., Stange, E.F. Am. J. Hum. Genet. (2006) [Pubmed]
  11. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. Voss, E., Wehkamp, J., Wehkamp, K., Stange, E.F., Schröder, J.M., Harder, J. J. Biol. Chem. (2006) [Pubmed]
  12. Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Niyonsaba, F., Someya, A., Hirata, M., Ogawa, H., Nagaoka, I. Eur. J. Immunol. (2001) [Pubmed]
  13. NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Wehkamp, J., Harder, J., Wehkamp, K., Wehkamp-von Meissner, B., Schlee, M., Enders, C., Sonnenborn, U., Nuding, S., Bengmark, S., Fellermann, K., Schröder, J.M., Stange, E.F. Infect. Immun. (2004) [Pubmed]
  14. Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Niyonsaba, F., Iwabuchi, K., Matsuda, H., Ogawa, H., Nagaoka, I. Int. Immunol. (2002) [Pubmed]
  15. Structure of the lysosomal sphingolipid activator protein 1 by homology with influenza virus neuraminidase. Potier, M. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  16. Distribution of human beta-defensin polymorphisms in various control and cystic fibrosis populations. Vankeerberghen, A., Scudiero, O., De Boeck, K., Macek, M., Pignatti, P.F., Van Hul, N., Nuytten, H., Salvatore, F., Castaldo, G., Zemkova, D., Vavrova, V., Cassiman, J.J., Cuppens, H. Genomics (2005) [Pubmed]
  17. Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23. Linzmeier, R.M., Ganz, T. Genomics (2005) [Pubmed]
  18. Expression and activity of beta-defensins and LL-37 in the developing human lung. Starner, T.D., Agerberth, B., Gudmundsson, G.H., McCray, P.B. J. Immunol. (2005) [Pubmed]
  19. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. Kao, C.Y., Chen, Y., Thai, P., Wachi, S., Huang, F., Kim, C., Harper, R.W., Wu, R. J. Immunol. (2004) [Pubmed]
  20. Antimicrobial peptides are present in immune and host defense cells of the human respiratory and gastroinstestinal tracts. Wah, J., Wellek, A., Frankenberger, M., Unterberger, P., Welsch, U., Bals, R. Cell Tissue Res. (2006) [Pubmed]
  21. Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree. Harada, K., Ohba, K., Ozaki, S., Isse, K., Hirayama, T., Wada, A., Nakanuma, Y. Hepatology (2004) [Pubmed]
  22. Human {alpha}- and beta-Defensins Block Multiple Steps in Herpes Simplex Virus Infection. Hazrati, E., Galen, B., Lu, W., Wang, W., Ouyang, Y., Keller, M.J., Lehrer, R.I., Herold, B.C. J. Immunol. (2006) [Pubmed]
  23. Actinobacillus actinomycetemcomitans outer membrane protein 100 triggers innate immunity and production of beta-defensin and the 18-kilodalton cationic antimicrobial protein through the fibronectin-integrin pathway in human gingival epithelial cells. Ouhara, K., Komatsuzawa, H., Shiba, H., Uchida, Y., Kawai, T., Sayama, K., Hashimoto, K., Taubman, M.A., Kurihara, H., Sugai, M. Infect. Immun. (2006) [Pubmed]
  24. Use of human reconstructed epidermis to analyze the regulation of beta-defensin hBD-1, hBD-2, and hBD-3 expression in response to LPS. Chadebech, P., Goidin, D., Jacquet, C., Viac, J., Schmitt, D., Staquet, M.J. Cell Biol. Toxicol. (2003) [Pubmed]
  25. Transcriptional regulation of beta-defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells. Mineshiba, J., Myokai, F., Mineshiba, F., Matsuura, K., Nishimura, F., Takashiba, S. FEMS Immunol. Med. Microbiol. (2005) [Pubmed]
  26. NF-kappa B-mediated transcriptional regulation of human beta-defensin-2 gene following lipopolysaccharide stimulation. Tsutsumi-Ishii, Y., Nagaoka, I. J. Leukoc. Biol. (2002) [Pubmed]
  27. Correlation between beta-defensin expression and induction profiles in gingival keratinocytes. Joly, S., Organ, C.C., Johnson, G.K., McCray, P.B., Guthmiller, J.M. Mol. Immunol. (2005) [Pubmed]
  28. Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells. Moon, S.K., Lee, H.Y., Pan, H., Takeshita, T., Park, R., Cha, K., Andalibi, A., Lim, D.J. BMC Infect. Dis. (2006) [Pubmed]
  29. The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus. Schibli, D.J., Hunter, H.N., Aseyev, V., Starner, T.D., Wiencek, J.M., McCray, P.B., Tack, B.F., Vogel, H.J. J. Biol. Chem. (2002) [Pubmed]
  30. Airway epithelia regulate expression of human beta-defensin 2 through Toll-like receptor 2. Wang, X., Zhang, Z., Louboutin, J.P., Moser, C., Weiner, D.J., Wilson, J.M. FASEB J. (2003) [Pubmed]
 
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