Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission
Journal - The American Journal of Pathology
Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcR?III, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission.
Night/Day Changes in Pineal Expression of >600 Genes
Journal - Journal of Biological Chemistry
The pineal gland plays an essential role in vertebrate chronobiologyby converting time into a hormonal signal, melatonin, whichis always elevated at night. Here we have analyzed the rodentpineal transcriptome using Affymetrix GeneChip® technologyto obtain a more complete description of pineal cell biology.The effort revealed that 604 genes (1,268 probe sets) with EntrezGene identifiers are differentially expressed greater than 2-foldbetween midnight and mid-day (false discovery rate <0.20).Expression is greater at night in 70%. These findings were supportedby the results of radiochemical in situ hybridization histologyand quantitative real time-PCR studies. We also found that theregulatory mechanism controlling the night/day changes in theexpression of most genes involves norepinephrine-cyclic AMPsignaling. Comparison of the pineal gene expression profilewith that in other tissues identified 334 genes (496 probe sets)that are expressed greater than 8-fold higher in the pinealgland relative to other tissues. Of these genes, 17% are expressedat similar levels in the retina, consistent with a common evolutionaryorigin of these tissues. Functional categorization of the highlyexpressed and/or night/day differentially expressed genes identifiedclusters that are markers of specialized functions, includingthe immune/inflammation response, melatonin synthesis, photodetection,thyroid hormone signaling, and diverse aspects of cellular signalingand cell biology. These studies produce a paradigm shift inour understanding of the 24-h dynamics of the pineal gland fromone focused on melatonin synthesis to one including many cellularprocesses.Note Added in Proof—The Sertoli cell data used for calculatingmedian expression levels in experiment A were obtained fromRef. 126.* This work was supported, in whole or in part, by the NationalInstitutes of Health (NICHD, Intramural Research Program toM. J. B., S. L. C., J. K., Q. S., P. G., F. M., S. G., J. L.W., and D. C. K.; Center for Information Technology to Z. G.R. and P. J. M.). The costs of publication of this article weredefrayed in part by the payment of page charges. This articlemust therefore be hereby marked "advertisement" in accordancewith 18 U.S.C. Section 1734 solely to indicate this fact. The on-line version of this article (available at http://www.jbc.org)contains supplemental Procedures, Tables S1–S8, and Figs.S1 and S2.1 Present address: Dept. of Poultry Science, Texas A & M University,College Station, TX 77843.2 Supported by The Wellcome Trust.3 Present address: Laboratory of Molecular Neurophysiology, Dept.of Life Science, POSTECH, San 31 Hyoja-dong, Pohang, South Korea,790-784.4 Present address: OriGene Technologies Inc., 6 Taft Ct., Suite100, Rockville, MD 20850.5 Present address: INSERM U614, Laboratory of Molecular Genetics,Faculty of Medicine and University Hospital, Rouen, France.6 Present address: INSERM U413, Laboratory of Cellular and MolecularNeuroendocrinology, European Institute for Peptide Research,University of Rouen, Mont-Saint-Aignan, France.7 Present address: Institute of Molecular Medicine, New Delhi110020, India.8 Supported by NIMH P50 Conte Center Grant MH074924, NINDS GrantR01 NS054794, and Pennsylvania Commonwealth Health ResearchFormula funds. Present address: Dept. of Pharmacology and Institutefor Translational Medicine and Therapeutics, University of PennsylvaniaSchool of Medicine, 421 Curie Blvd., Philadelphia, PA 19104.9 Supported by The Lundbeck Foundation, Danish Medical ResearchCouncil Grants 271-07-0412 and 271-06-0754, The Novo NordiskFoundation, The Carlsberg Foundation, Fonden til LægevidenskabensFremme, and Simon Fougner Hartmanns Familiefond.10 Present address: Science Policy Branch, National Institute onDrug Abuse, Bethesda, MD 20892.11 Supported by Research Equipment Initiative Grant BB/D52503X/1from the Biotechnology and Biological Sciences Research Council.