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D. A. Sullivan, S. M. Richards; Sex and Hormone Influence on Surfactant Protein Gene Expression in Ocular Surface Tissues. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5283.
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Surfactant proteins (SPs) play a critical role in decreasing surface tension at the lung air-liquid interface, as well as in modulating pulmonary innate and adaptive immunity. These proteins include hydrophobic species that interact with lipids to reduce surface tension, and host defense-related SPs that are members of the collectin family. We hypothesize that SPs serve a similar function on the ocular surface and promote both tear film stability and immune defense. To begin to test this hypothesis, we examined whether the genes for SPs and their receptors, other collectins, and SP-associated proteins (e.g. transporters, enzymes) are expressed in mouse lacrimal and meibomian glands and human corneal epithelial cells. We also evaluated whether gene expression: [a] is influenced by sex and sex steroid hormones, given that these factors modulate lung surfactant production; and [b] occurs in mouse submandibular, parotid and sublingual tissues.
Lacrimal, meibomian and salivary glands were obtained from adult, male and female BALB/c, C57BL/6, MRL//Mp-lpr/lpr, non-obese diabetic and/or aromatase knockout mice that were either intact or castrated, and/or administered testosterone, estradiol-17beta, progesterone or placebo for 2 weeks. Human corneal epithelial cells were removed from the corneoscleral rims of male and female donors. Samples were processed for the identification of differentially expressed mRNAs by utilizing GE CodeLink Bioarrays and Affymetrix GeneChips, and data were statistically analyzed.
Our results show that the mRNAs for SPs (A1, A2, B, C & D) and their receptors (e.g. GP340, SIRPalpha, CD93, TLR2, TLR4, calreticulin, MD2, CD14, SPR-210, CD91), other collectins (e.g. MBLA, MBLC, sub-family members 10, 11 & 12) and SP-associated proteins (e.g. Esterase 1, ABCA3, Masp1, Masp2, ficolin A) are expressed in ocular and salivary tissues. In addition, our data demonstrate that the levels of many of these mRNAs are significantly up- or down-regulated by sex and sex steroids.
Our findings support our hypothesis that SPs may play multiple roles on the ocular surface. (We thank Roderick V. Jensen for his help. This research was supported by NIH grant EY05612)
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