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  • Letter to the Editor
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Reply to Mummidi et al.

Genes & Immunity volume 10, page 199 (2009)Cite this article

We are pleased that there is interest in our study1 Given the association of −2578 G with the advanced progression of several pathological conditions, understanding the transcriptional regulation of the −2578 single nucleotide polymorphism at a molecular level holds promise for strategic therapeutic intervention. The major finding reported in our paper was the identification of Prep1/Pbx2 complexes in an astrocytic cell line (classical producers of CCL2) that bind preferentially to the −2578 G allele.

The response to our paper by Mummidi et al. does not contest the evidence supporting our conclusions regarding Prep1/Pbx2, but rather focuses on the lack of evidence our data provided for the binding of interferon regulatory factor-1 (IRF-1) to −2578 A (or G) and hence interferon stimulatory response element (ISRE) activity of the −2578 single nucleotide polymorphism. Earlier, this group showed in supplemental data to Gonzalez et al.2 that IRF-1 in nuclear extracts from the MG-63 osteoblastic cell line binds preferentially to the −2578 A allele. In the extended study accompanying their letter, they demonstrate that in vitro transcribed and translated IRF-1 can bind to −2578 A oligos including the −2578 A oligo used in our report. It is their view that the ability of in vitro transcribed and translated IRF-1 to bind −2578 A oligos indicates that the −2578 region functions as an ISRE, and as a consequence, the opposite conclusion reached in our study may need revision.

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References

  1. Wright Jr EK, Page SH, Barber SA, Clements JE . Prep1/Pbx2 complexes regulate CCL2 expression through the −2578 guanine polymorphism. Genes Immun 2008; 9: 419–430.

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  2. Gonzalez E, Rovin BH, Sen L, Cooke G, Dhanda R, Mummidi S et al. HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci USA 2002; 99: 13795–13800.

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Authors and Affiliations

  1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    E K Wright Jr & S H Page

  2. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    E K Wright Jr, S H Page & J E Clements

  3. Booz Allen Hamilton, Rockville, MD, USA

    S A Barber

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  1. E K Wright Jr
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  2. S H Page
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  3. S A Barber
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  4. J E Clements
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Correspondence to J E Clements.

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Wright, E., Page, S., Barber, S. et al. Reply to Mummidi et al.. Genes Immun 10, 199 (2009). https://doi.org/10.1038/gene.2008.76

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