Department of Dermatology

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Browsing Department of Dermatology by Author "Al-Hassani, Mohammed"

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    Chemotherapeutic agents subvert tumor immunity by generating agonists of platelet-activating factor
    (American Association for Cancer Research, 2014-12-01) Sahu, Ravi P.; Ocana, Jesus A.; Harrison, Kathleen A.; Ferracini, Matheus; Touloukian, Christopher E.; Al-Hassani, Mohammed; Sun, Louis; Loesch, Mathew; Murphy, Robert C.; Althouse, Sandra K.; Perkins, Susan M.; Speicher, Paul J.; Tyler, Douglas S.; Konger, Raymond L.; Travers, Jeffrey B.; Department of Dermatology, IU School of Medicine
    Oxidative stress suppresses host immunity by generating oxidized lipid agonists of the platelet-activating factor receptor (PAF-R). Because many classical chemotherapeutic drugs induce reactive oxygen species (ROS), we investigated whether these drugs might subvert host immunity by activating PAF-R. Here, we show that PAF-R agonists are produced in melanoma cells by chemotherapy that is administered in vitro, in vivo, or in human subjects. Structural characterization of the PAF-R agonists induced revealed multiple oxidized glycerophosphocholines that are generated nonenzymatically. In a murine model of melanoma, chemotherapeutic administration could augment tumor growth by a PAF-R-dependent process that could be blocked by treatment with antioxidants or COX-2 inhibitors or by depletion of regulatory T cells. Our findings reveal how PAF-R agonists induced by chemotherapy treatment can promote treatment failure. Furthermore, they offer new insights into how to improve the efficacy of chemotherapy by blocking its heretofore unknown impact on PAF-R activation.
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    Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis
    (Springer, 2018-04) DaSilva-Arnold, Sonia C.; Thyagarajan, Anita; Seymour, Leroy J.; Yi, Qiaofang; Bradish, Joshua R.; Al-Hassani, Mohammed; Zhou, Hongming; Perdue, Nikolajs J.; Nemmeth, Val; Krbanjevic, Aleksandar; Serezani, Ana P. M.; Olson, Matthew R.; Spandau, Dan F.; Travers, Jeffrey B.; Kaplan, Mark H.; Turner, Matthew J.; Dermatology, School of Medicine
    The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system.