Re: Cytokine Storm & Vitamin D relationship?
http://www.jimmunol.org/cgi/content/abstract/179/4/2060
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The Journal of Immunology, 2007, 179, 2060 -2063
Copyright ? 2007 by
The American Association of Immunologists, Inc. [/SIZE]
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Cutting Edge: Vitamin D-Mediated Human Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on the Induction of Cathelicidin<SUP>1</SUP>
</NOBR><NOBR>Philip T. Liu<SUP>*</SUP></NOBR>, <NOBR>Steffen Stenger<SUP></SUP></NOBR>, <NOBR>Dominic H. Tang<SUP>*</SUP></NOBR> and <NOBR>Robert L. Modlin<SUP>2</SUP><SUP>,*</SUP></NOBR>
[SIZE=-1]<SUP>*</SUP> Division of Dermatology, Department of Medicine, and Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and <SUP>
</SUP> Institute for Medical Microbiology and Hygiene, University of Ulm, Ulm, Germany [/SIZE]
<!-- ABS -->Host defense against intracellular pathogens depends upon innate<SUP> </SUP>and adaptive antimicrobial effector pathways. TLR2/1-activation<SUP> </SUP>of monocytes leads to the vitamin D-dependent production of<SUP> </SUP>cathelicidin and, at the same time, an antimicrobial activity<SUP> </SUP>against intracellular
Mycobacterium tuberculosis. To determine<SUP> </SUP>whether induction of cathelicidin was required for the vitamin<SUP> </SUP>D-triggered antimicrobial activity, the human monocytic cell<SUP> </SUP>line THP-1 was infected with
M. tuberculosis H37Ra and then<SUP> </SUP>activated with the active vitamin D hormone 1,25-dihydroxyvitamin<SUP> </SUP>D<SUB>3</SUB> (1,25D<SUB>3</SUB>). 1,25D<SUB>3</SUB> stimulation resulted in antimicrobial activity<SUP> </SUP>against intracellular
M. tuberculosis and expression of cathelicidin<SUP> </SUP>mRNA and protein. Using small interfering RNA (siRNA) specific<SUP> </SUP>for cathelicidin, 1,25D<SUB>3</SUB>-induced cathelicidin mRNA and protein<SUP> </SUP>expressions were efficiently knocked down, whereas a nonspecific<SUP> </SUP>siRNA control had little effect. Finally, 1,25D<SUB>3</SUB>-induced antimicrobial<SUP> </SUP>activity was completely inhibited in the presence of siRNA against<SUP> </SUP>cathelicidin, instead leading to enhanced intracellular growth<SUP> </SUP>of mycobacteria. These data demonstrate that cathelicidin is<SUP> </SUP>required for the 1,25D<SUB>3</SUB>-triggered antimicrobial activity against<SUP> </SUP>intracellular
M. tuberculosis.<SUP> </SUP>
<!-- FN --><!-- null -->The costs of publication of this article were defrayed in part<SUP> </SUP>by the payment of page charges. This article must therefore<SUP> </SUP>be hereby marked
advertisement in accordance with 18 U.S.C.<SUP> </SUP>Section 1734 solely to indicate this fact.<SUP> </SUP>
<!-- null --><SUP>1</SUP> This work was supported in part by National Institutes of Health<SUP> </SUP>Grants R01 AI22553, R01 AI47868, and R01 AR40312. P.T.L. is<SUP> </SUP>supported by Microbial Pathogenesis Training Grant 2-T32-AI-07323.<SUP> </SUP>S.S. is funded by Deutsche Forschungsgemeinschaft SFB 643.<SUP> </SUP>
<!-- null --><SUP>2</SUP> Address correspondence and reprint requests to Dr. Robert L.<SUP> </SUP>Modlin, Division of Dermatology, University of California Los<SUP> </SUP>Angeles, 52-121 Center for the Health Sciences, 10833 Le Conte<SUP> </SUP>Avenue, Los Angeles, CA 90095. E-mail address:
rmodlin@mednet.ucla.edu<SCRIPT type=text/javascript><!-- var u = "rmodlin", d = "mednet.ucla.edu"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></SCRIPT> <SUP></SUP><!-- null --><SUP>3</SUP> Abbreviations used in this paper: 1,25D<SUB>3</SUB>, 1,25-dihydroxyvitamin<SUP> </SUP>D<SUB>3</SUB>; MOI, multiplicity of infection; qPCR, quantitative PCR;<SUP> </SUP>siRNA, small interfering RNA; siCath, siRNA specific for the<SUP> </SUP>cathelicidin gene; ciCTRL, nonspecific siRNA control oligo.<SUP> </SUP>