Browsing by Author "Paul Mozdziak, Committee Member"

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    Host Cytokines and Immune Responses in Pregnancy Associated Transmission of Arrested Hookworm Larvae
    (2006-09-30) Trivedi, Shweta; Prema Arasu, Committee Chair; William Miller, Committee Member; Paul Mozdziak, Committee Member; Scott Laster, Committee Member
    Over one billion people worldwide are infected with blood-feeding intestinal hookworms. The life cycle of A. duodenale (humans) and A. caninum (dogs) includes the propensity for L3 to undergo a temporary state of developmental arrest in the host. In female hosts, tissue-arrested L3 reactivate during pregnancy and are transmitted to neonates through milk. During pregnancy, transforming growth factor (TGF)-β2 is upregulated in the mammary gland. Studies in C. elegans show that TGF-β and insulin-like signaling pathways regulate larval arrest and reactivation. We previously utilized an in vitro assay to demonstrate that recombinant human TGF-β stimulates a feeding response in tissue-arrested A. caninum L3. We hypothesize that host expression of TGF-β and pregnancy hormones such as estrogen and prolactin signal arrested L3 to reactivate. To facilitate in vivo analyses, we utilized a mouse model of A. caninum infection. Mice were utilized because L3 do not develop into adults but arrest in somatic tissues, and reactivate during the periparturient period. We investigated TGF-β1, TGF-β2 and IGF-1 transcript and serum cytokine profiles during late pregnancy, early lactation and mid-lactation to correlate levels with transmammary transmission of L3 to nursing pups. An in vitro co-culture system was developed to mimic in vivo conditions and assess effects of TGF-β and, estrogen and prolactin on larval reactivation. A. caninum L3 were co-incubated with skeletal muscle or mammary epithelial cells and larval reactivation was measured. Additionally, immune responses were assessed as by measuring serum and transcript levels of IFN-γ and IL-4 in skeletal muscle, mammary gland and spleen to dissect the effects of pregnancy and A. caninum infection in the mouse. Our findings suggest that host-derived TGF- β1 and IGF-1, but not TGF- β2, are important in reactivation and transmission of arrested A. caninum larvae. Also, a Th2-like response characterized by increased IL-4 transcript levels was observed in skeletal muscle, while a mixed Th1⁄Th2 profile was observed in mammary gland when comparing infection with A. caninum versus pregnancy/lactation in BALB⁄c mice.
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    Salinity Regulation of Prolactin Cell Proliferation and Apoptosis in the Euryhaline Teleost, the Tilapia (Oreochromis mossambicus).
    (2008-12-09) Strom, Chrisitna Nelson; Russell Borski, Committee Chair; Heather Patisaul, Committee Member; Paul Mozdziak, Committee Member
    The euryhaline tilapia, Oreochromis mossambicus, has the ability to live in both freshwater (FW) and saltwater (SW) environments. Prolactin (PRL) is the most critical hormone to promoting life in FW, and without it tilapia loses the capacity to osmoregulate in hypotonic environments. Consistent with PRL’s actions in FW adaptation, pituitary PRL synthesis, content, secretion, and cell activity are all elevated in FW compared to SW acclimated tilapia We found that the PRL region of a FW tilapia pituitary has a 3-fold larger volume than the PRL region of a SW pituitary. It is unclear whether this increased tissue volume is due to larger cells (hypertrophy) or more cells (hyperplasia). Therefore, we evaluated if PRL cell proliferation and apoptosis might be sensitive to salinity and could account for the greater abundance of PRL in FW versus SW fish. Freshwater tilapia were transferred to either SW or sham transferred to FW and SW fish were moved to either FW or SW over a time course of 7 days. Pituitaries were sampled over the course of salinity challenge and triple stained for determination of lactotroph cell density (nuclei staining with Hoescht dye), proliferation (BrdU labeling) and apoptosis (TUNEL assay). Lactotrophs were identified by immunostaining using tilapia specific PRL antisera. Lactotroph cell densities were 40% lower in FW than SW fish and declined when fish were transferred from SW to FW (P < 0.001). The larger volume of the PRL cell region within the pituitary area combined with lower number of lactotrophs per unit area suggests that the cells are larger in FW than SW acclimated fish. There were negligible levels of apoptosis in lactotrophs and salinity was ineffective in regulating programmed cell death. By contrast, we found a dramatic effect of salinity on lactotroph cell proliferation. The pituitaries of FW tilapia show a higher rate of PRL cell proliferation than those of SW fish. During transfer from SW to FW proliferation increased by almost 20-fold compared with controls (P < 0.001). When fish were transferred from FW to SW, proliferation declined within 1 day to levels observed in sham transferred SW fish. The enhanced proliferation combined with increased volume of the pituitary PRL cell region, decline in lactotroph cell density, and presumed increase in cell volume, suggests that the tilapia lactotroph undergoes hypertrophy and hyperplasia in FW environments. Apoptosis appears to play little role in regulating lactotroph density under different salinities. Overall, these results suggest that the elevated production and content of PRL critical to life in FW is mediated, in part, through enhanced lactotroph proliferation and hypertrophy.