Vitamin D and molecular actions on the immune system: Modulation of innate and autoimmunity

Journal of Molecular Medicine

Volumn 88, Issue 5, 2010, Pages 441-450

  Kamen, Diane L ^a   Tangpricha, Vin ^b,c,d  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c EMORY UNIVERSITY   (United States)

^d 101 Woodruff Circle NE WMRB 1301 ^*  (United States)

Author keywords

Immunology; Innate immunity; Vitamins

Indexed keywords

BETA DEFENSIN; CATHELICIDIN; COD LIVER OIL; COLECALCIFEROL; ERGOCALCIFEROL; GAMMA INTERFERON; TOLL LIKE RECEPTOR 2; VITAMIN D; VITAMIN D RECEPTOR;

ADAPTIVE IMMUNITY; ANTIMICROBIAL ACTIVITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; BLOOD LEVEL; CANCER CELL; CELL FUNCTION; DENDRITIC CELL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOMODULATION; IMMUNOREGULATION; INFLUENZA; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; LUNG ADENOCARCINOMA; MOLECULAR EVOLUTION; NONHUMAN; PHENOTYPE; RECEPTOR UPREGULATION; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION; TUBERCULOSIS; ULTRAVIOLET RADIATION; UPPER RESPIRATORY TRACT INFECTION; VAGINITIS; VITAMIN D DEFICIENCY; VITAMIN D RESPONSIVE ELEMENT; VITAMIN METABOLISM; VITAMIN SUPPLEMENTATION;

ADAPTIVE IMMUNITY; ANIMALS; AUTOIMMUNE DISEASES; AUTOIMMUNITY; HUMANS; IMMUNITY, INNATE; VITAMIN D;

EID: 77954562871     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00109-010-0590-9     Document Type: Review

References (115)

1. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357 (3):266-281
2. 3 target genes. Mol Endocrinol 19 (11):2685-2695
3. 3 production. Endocrinology 148 (7):3410-3418
4. Cross HS (2007) Extrarenal vitamin D hydroxylase expression and activity in normal and malignant cells: modification of expression by epigenetic mechanisms and dietary substances. Nutr Rev 65 (8 Pt 2): S108-S112
5. Williams CJB (1849) On the use and administration of cod-liver oil in pulmonary consumption. London Journal of Medicine 1:1-18
6. Finsen NR (1903) Nobel prize presentation speech by professor the count K. A. H. Morner, Rector of the Royal Caroline Institute on December 10, 1903. www.nobelprize.org
7. Moller KI, Kongshoj B, Philipsen PA, Thomsen VO, Wulf HC (2005) How Finsen's light cured lupus vulgaris. Photodermatol Photoimmunol Photomed 21 (3):118-124
8. Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ (2007) Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol 103 (3-5): 793-798
9. 3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57 (1):159-163
10. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik S et al (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science; 311:1773-3
11. Trinchieri G, Sher A (2007) Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 7 (3):179-190
12. Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449 (7164):819-826
13. Ramanathan B, Davis EG, Ross CR, Blecha F (2002) Cath-elicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect 4 (3):361-372
14. Weber G, Heilborn JD, Chamorro Jimenez CI, Hammarsjo A, Torma H, Stahle M (2005) Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol 124 (5):1080-1082
15. Bals R, Wang X, Zasloff M, Wilson JM (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA 95 (16):9541-9546
16. Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L et al (1997) Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. J Biol Chem 272 (20):13088-13093
17. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L et al (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96 (9):3086-3093
18. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J et al (2004) Cutting edge: 1, 25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173 (5):2909-2912
19. Gombart AF, Saito T, Koeffler HP (2009) Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune responseinhumans and primates. BMC Genomics 10:321
20. Gombart AF, Borregaard N, Koeffler HP (2005) Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1, 25-dihydroxyvitamin D3. Faseb J 19 (9):1067-1077
21. 3 in various tissues. J Steroid Biochem Mol Biol 103 (3-5): 552-557
22. Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D et al (2007) Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117 (3):803-811
23. 3 in human skin equivalents. Exp Dermatol 9 (2):97-103
24. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S et al (2006) Epidemic influenza and vitamin D. Epidemiol Infect 134 (6):1129-1140
25. Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamaki H et al (2007) An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr 86 (3):714-717
26. Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH et al (2008) Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic. Ann Otol Rhinol Laryngol 117 (11):864-870
27. Ginde AA, Mansbach JM, Camargo CA Jr (2009) Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 169 (4):384-390
28. Villamor E (2006) A potential role for vitamin D on HIV infection? Nutr Rev 64 (5 Pt 1):226-233
29. Bodnar LM, Krohn MA, Simhan HN (2009) Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr 139 (6):1157-1161
30. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR et al (2009) Alterations in vitamin D status and antimicrobial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 7:28
31. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA Jr, Koeffler HP et al (2009) Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis 48 (4):418-424
32. Yamshchikov AV, Desai NS, Blumberg HM, Ziegler TR, Tangpricha V (2009) Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials. Endocr Pract 15 (5):438-449
33. Nnoaham KE, Clarke A (2008) Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol 37 (1):113-119
34. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM et al (2009) Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 179 (9):843-850
35. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF et al (2009) Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 182 (7):4289-4295
36. Yamshchikov AV, Oladele A, Leonard MK Jr, Blumberg HM, Ziegler TR, Tangpricha V (2010) Vitamin D as Adjunctive Therapy in Refractory Pulmonary Tuberculosis: A Case Report. South Med J. in press
37. Loomis WF (1967) Skin-pigment regulation of vitamin-D biosynthesis in man. Science 157 (788):501-506
38. Chaplin G, Jablonski NG (2009) Vitamin D and the evolution of human depigmentation. Am J Phys Anthropol 139 (4):451-461
39. Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF (2009) Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab 94 (3):940-945
40. Kappelman J, Alcicek MC, Kazanci N, Schultz M, Ozkul M, Sen S (2008) First Homo erectus from Turkey and implications for migrations into temperate Eurasia. Am J Phys Anthropol 135 (1):110-116
41. Dib J, Motok J, Zenoff VF, Ordonez O, Farias ME (2008) Occurrence of resistance to antibiotics, UV-B, and arsenic in bacteria isolated from extreme environments in high-altitude (above 4400 m) Andean wetlands. Curr Microbiol 56 (5):510-517
42. Kamen D, Aranow C (2008) Vitamin D in systemic lupus erythematosus. Curr Opin Rheumatol 20 (5):532-537
43. Deluca HF, Cantorna MT (2001) Vitamin D: its role and uses in immunology. Faseb J 15 (14):2579-2585
44. Arnson Y, Amital H, Shoenfeld Y (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 66 (9):1137-1142
45. Norman AW (2006) Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology 147 (12):5542-5548
46. Veldman CM, Cantorna MT, DeLuca HF (2000) Expression of 1, 25-dihydroxyvitamin D (3) receptor in the immune system. Arch Biochem Biophys 374 (2):334-338
47. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE (2007) Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179 (3):1634-1647
48. van Etten E, Stoffels K, Gysemans C, Mathieu C, Overbergh L (2008) Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 66 (10 Suppl 2): S125-S134
49. Correale J, Ysrraelit MC, Gaitan MI (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132 (Pt 5):1146-1160
50. Mahon BD, Wittke A, Weaver V, Cantorna MT (2003) The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem 89 (5):922-932
51. Bhalla AK, Amento EP, Serog B, Glimcher LH (1984) 1, 25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol 133 (4):1748-1754
52. Mattner F, Smiroldo S, Galbiati F, Muller M, Di Lucia P, Poliani PL et al (2000) Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1, 25-dihydroxyvitamin D (3). Eur J Immunol 30 (2):498-508
53. 3: preferential inhibition of Th1 functions. J Nutr 125 (6 Suppl): 1704S-1708S
54. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O'Garra A (2001) 1alpha, 25-Dihydroxyvitamin d3 has a direct effect on naive CD4 (+) T cells to enhance the development of Th2 cells. J Immunol 167 (9):4974-4980
55. 3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543). Diabetes 49 (8):1301-1307
56. Staeva-Vieira TP, Freedman LP (2002) 1, 25-dihydroxyvitamin D3 inhibits IFN-gamma and IL-4 levels during in vitro polarization of primary murine CD4+ T cells. J Immunol 168 (3):1181-1189
57. 3. Blood 106 (10):3490-3497
58. Eisenstein EM, Williams CB (2009) The T (reg)/Th17 cell balance: a new paradigm for autoimmunity. Pediatr Res 65 (5 Pt 2):26R-31R
59. Tang J, Zhou R, Luger D, Zhu W, Silver PB, Grajewski RS et al (2009) Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response. J Immunol 182 (8):4624-4632
60. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM (2008) Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther 324 (1):23-33
61. 3 inhibits pro-inflammatory cytokine and chemokine expression in human corneal epithelial cells colonized with Pseudomonas aeruginosa. Immunol Cell Biol 80 (4):340-345
62. van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB et al (2007) The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol 37 (2):395-405
63. 3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol 167 (4):1945-1953
64. Smolders J, Thewissen M, Peelen E, Menheere P, Cohen Tervaert JW, Damoiseaux J et al (2009) Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS ONE 4 (8): e6635
65. 3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest 74 (2):657-661
66. Linker-Israeli M, Elstner E, Klinenberg JR, Wallace DJ, Koeffler HP (2001) Vitamin D (3) and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC. Clin Immunol 99 (1):82-93
67. 3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci USA 98 (12):6800-6805
68. 3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype. J Immunol 182 (4):2074-2083
69. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392 (6673):245-252
70. Lanzavecchia A, Sallusto F (2001) Regulation of T cell immunity by dendritic cells. Cell 106 (3):263-266
71. 3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun 23 (3):233-239
72. 3 on type I IFN-mediated monocyte differentiation into dendritic cells: impairment of functional activities and chemotaxis. J Immunol 174 (1):270-276
73. 3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 164 (9):4443-4451
74. 3 (1, 25 (OH) (2) D (3)) hampers the maturation of fully active immature dendritic cells from monocytes. Eur J Endocrinol 145 (3):351-357
75. Van Amerongen BM, Dijkstra CD, Lips P, Polman CH (2004) Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr; 58:1095-1109
76. 3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 93 (15):7861-7864
77. 3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone. Bone 32 (4):397-404
78. Cantorna MT, Hayes CE, DeLuca HF (1998) 1, 25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 128 (1):68-72
79. Larsson P, Mattsson L, Klareskog L, Johnsson C (1998) A vitamin D analogue (MC 1288) has immunomodulatory properties and suppresses collagen-induced arthritis (CIA) without causing hyper-calcaemia. Clin Exp Immunol 114 (2):277-283
80. Zella JB, McCary LC, DeLuca HF (2003) Oral administration of 1, 25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Arch Biochem Biophys 417 (1):77-80
81. Giulietti A, Gysemans C, Stoffels K, van Etten E, Decallonne B, Overbergh L et al (2004) Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice. Diabetologia 47 (3):451-462
82. 3. Diabetologia 37 (6):552-558
83. Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT (2003) A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 17 (12):2386-2392
84. Cantorna MT, Munsick C, Bemiss C, Mahon BD (2000) 1, 25- Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr 130 (11):2648-2652
85. 3 administration on lymphoproliferation and autoimmune disease in MRL/MP-lpr/lpr mice. Int Arch Allergy Appl Immunol 77 (4):396-404
86. 3 attenuates the expression of experimental murine lupus of MRL/l mice. Autoimmunity 12 (2):143-148
87. Nielen MM, van Schaardenburg D, Lems WF, van de Stadt RJ, de Koning MH, Reesink HW et al (2006) Vitamin D deficiency does not increase the risk of rheumatoid arthritis: comment on the article by Merlino et al. Arthritis Rheum 54 (11):3719-3720
88. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG (2004) Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis Rheum 50 (1):72-77
89. Costenbader KH, Feskanich D, Benito-Garcia E, Holmes M, Karlson E (2007) Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis; 67:530-5
90. Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D (2007) Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 56 (7):2143-2149
91. Cutolo M, Otsa K, Laas K, Yprus M, Lehtme R, Secchi ME et al (2006) Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 24 (6):702-704
92. Munger KL, Zhang SM, O'Reilly E, Hernan MA, Olek MJ, Willett WC et al (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62 (1):60-65
93. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. Jama 296 (23):2832-2838
94. Embry AF, Snowdon LR, Vieth R (2000) Vitamin D and seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 48 (2):271-272
95. Tremlett H, van der Mei IA, Pittas F, Blizzard L, Paley G, Mesaros D et al (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 31 (4):271-279
96. van der Mei IA, Blizzard L, Ponsonby AL, Dwyer T (2006) Validity and reliability of adult recall of past sun exposure in a case-control study of multiple sclerosis. Cancer Epidemiol Biomarkers Prev 15 (8):1538-1544
97. Zipitis CS, Akobeng AK (2008) Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child 93 (6):512-517
98. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358 (9292):1500-1503
99. Crow MK (2007) Type I interferon in systemic lupus erythematosus. Curr Top Microbiol Immunol 316:359-386
100. Ronnblom L, Eloranta ML, Alm GV (2006) The type I interferon system in systemic lupus erythematosus. Arthritis Rheum 54 (2):408-420
101. 3 and its analogs: physiologic and therapeutic implications for dendritic cell function. J Biol Chem 278 (49):49378-49385
102. Kamen DL, Aranow C (2008) The link between vitamin D deficiency and systemic lupus erythematosus. Curr Rheumatol Rep 10 (4):273-280
103. Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS (2006) Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 5 (2):114-117
104. 3 levels in prednisone-treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand 68 (1):109-111
105. 3 in patients with systemic lupus erythematosus. Clin Rheumatol 14 (4):397-400
106. Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia E (2008) Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 67 (4):530-535
107. Niyonsaba F, Hirata M, Ogawa H, Nagaoka I (2003) Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells. Curr Drug Targets Inflamm Allergy 2 (3):224-231
108. Lazarus R, Klimecki WT, Raby BA, Vercelli D, Palmer LJ, Kwiatkowski DJ et al (2003) Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U. S. ethnic groups and exploratory case-control disease association studies. Genomics 81 (1):85-91
109. Niyonsaba F, Ogawa H, Nagaoka I (2004) Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 111 (3):273-281
110. 3 is a potent suppressor of interferon gamma-mediated macrophage activation. Blood 106 (13):4351-4358
111. Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H (2005) The human beta-defensins (-1,-2,-3,-4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J Immunol 175 (3):1776-1784
112. Niyonsaba F, Nagaoka I, Ogawa H (2006) Human defensins and cathelicidins in the skin: beyond direct antimicrobial properties. Crit Rev Immunol 26 (6):545-576
113. Byers S, Shah S (2007) Vitamin D and the regulation of Wnt/beta-catenin signaling and innate immunity in colorectal cancer. Nutr Rev 65 (8 Pt 2): S118-S120
114. Chen X, Niyonsaba F, Ushio H, Hara M, Yokoi H, Matsumoto K et al (2007) Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. Eur J Immunol 37 (2):434-444
115. 3 as pluripotent immunomodulators. J Cell Biochem 88 (2):223-226