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81.
McLaughlin PJ Keiper CL Verderame MF Zagon IS 《American journal of physiology. Regulatory, integrative and comparative physiology》2012,302(9):R1084-R1090
The opioid growth factor (OGF) and its receptor, OGFr, play a regulatory role in cell proliferation, and maintain homeostasis through a tonically active negative feedback mechanism. To directly evaluate the repercussion of increased OGFr expression and consequent gain-of-function in epithelium, bovine keratin 5 promoter elements were used to direct the expression of OGFr to skin in a tetracycline-regulated manner. Three founder lines overexpressing OGFr (OGFrTG/K5-tTA) were established. Evidence for increased OGFr in the epithelium included a three-fold increase in OGFr binding activity, as well as significant increases in OGFr protein, as monitored by semiquantitative immunohistochemistry. DNA synthesis in target epithelium, including cornea, tongue, and skin of transgenic mice was decreased 41% to 80% from wild-type littermates; the liver, a nonepithelial organ, was not altered. Decreased DNA synthesis in corneal epithelium induced by transgenic expression of OGFr was further reduced by treatment with exogenous OGF but reversed by exposure to the opioid antagonist, naloxone. The number of cell layers in both epidermis and cornea of OGFrTG/K5-tTA animals was reduced nearly 45% from wild-type mice. Full-thickness wounds in mice overexpressing OGFr healed 37% to 75% slower than wild-type littermates. These data demonstrate for the first time that stable genetic amplification of OGFr downregulates homeostatic cell proliferation, as well as pathophysiological processes with respect to wound repair. These mice also can serve as a valuable model to dissect the mechanism of OGF-OGFr action and may be important in understanding the etiology, pathogenesis, and treatment of epithelium-related diseases. 相似文献
82.
Haymaker CL Guloglu FB Cascio JA Hardaway JC Dhakal M Wan X Hoeman CM Zaghouani S Rowland LM Tartar DM VanMorlan AM Zaghouani H 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(7):3208-3216
The earliest thymic progenitors (ETPs) were recently shown to give rise to both lymphoid and myeloid cells. Whereas the majority of ETPs are derived from IL-7Rα-positive cells and give rise exclusively to T cells, the origin of the myeloid cells remains undefined. In this study, we show both in vitro and in vivo that IL-13Rα1(+) ETPs yield myeloid cells with no potential for maturation into T cells, whereas IL-13Rα1(-) ETPs lack myeloid potential. Moreover, transfer of lineage-negative IL-13Rα1(+) bone marrow stem cells into IL-13Rα1-deficient mice reconstituted thymic IL-13Rα1(+) myeloid ETPs. Myeloid cells or macrophages in the thymus are regarded as phagocytic cells whose function is to clear apoptotic debris generated during T cell development. However, the myeloid cells derived from IL-13Rα1(+) ETPs were found to perform Ag-presenting functions. Thus, IL-13Rα1 defines a new class of myeloid restricted ETPs yielding APCs that could contribute to development of T cells and the control of immunity and autoimmunity. 相似文献
83.
KG Anderson H Sung CN Skon L Lefrancois A Deisinger V Vezys D Masopust 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(6):2702-2706
Nonlymphoid T cell populations control local infections and contribute to inflammatory diseases, thus driving efforts to understand the regulation of their migration, differentiation, and maintenance. Numerous observations indicate that T cell trafficking and differentiation within the lung are starkly different from what has been described in most nonlymphoid tissues, including intestine and skin. After systemic infection, we found that >95% of memory CD8 T cells isolated from mouse lung via standard methods were actually confined to the pulmonary vasculature, despite perfusion. A respiratory route of challenge increased virus-specific T cell localization within lung tissue, although only transiently. Removing blood-borne cells from analysis by the simple technique of intravascular staining revealed distinct phenotypic signatures and chemokine-dependent trafficking restricted to Ag-experienced T cells. These results precipitate a revised model for pulmonary T cell trafficking and differentiation and a re-evaluation of studies examining the contributions of pulmonary T cells to protection and disease. 相似文献
84.
Caulobacter crescentus differentiates from a motile, foraging swarmer cell into a sessile, replication-competent stalked cell during its cell cycle. This developmental transition is inhibited by nutrient deprivation to favor the motile swarmer state. We identify two cell cycle regulatory signals, ppGpp and polyphosphate (polyP), that inhibit the swarmer-to-stalked transition in both complex and glucose-exhausted media, thereby increasing the proportion of swarmer cells in mixed culture. Upon depletion of available carbon, swarmer cells lacking the ability to synthesize ppGpp or polyP improperly initiate chromosome replication, proteolyze the replication inhibitor CtrA, localize the cell fate determinant DivJ, and develop polar stalks. Furthermore, we show that swarmer cells produce more ppGpp than stalked cells upon starvation. These results provide evidence that ppGpp and polyP are cell-type-specific developmental regulators. 相似文献
85.
Cara A. Augustenborg John Finnan Leah McBennett Vivienne Connolly Uta Priegnitz Christoph Müller 《Global Change Biology Bioenergy》2012,4(5):597-610
A survey of Irish farmers was conducted to identify farmers’ opinions on energy crop production and to characterize potential adopters of energy crop cultivation in Ireland. One hundred and seventy‐two surveys were completed from 25 counties in Ireland. Miscanthus (48%) and grass (30%) were the preferred crops for adoption of energy crop production. Potential adopters described themselves as having a significantly greater level of knowledge of energy crop production compared with other respondents. The results indicate that lack of interest in adopting energy crop production may be due to lack of knowledge regarding the economic benefits of adoption and the variety of energy crops available for cultivation in Ireland. The establishment of long‐term contracts and government schemes were identified as important requirements for the development of bioenergy crop production in Ireland. Energy crop adoption was not limited to farmers undertaking specific farm enterprises. Farmers were motivated to adopt energy crop production for both economic and environmental benefits. These results are the first to provide valuable information on the perspectives of potential adopters of bioenergy crop production in Ireland for the promotion and implementation of a national bioenergy industry. Policy requirements and outreach strategies to encourage adoption of energy crops by agricultural producers are suggested. 相似文献
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