Article

Pleiotropy and redundancy of STAT proteins in early pregnancy.

Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
Reproduction in Domestic Animals (Impact Factor: 1.39). 09/2007; 42(4):343-53. DOI: 10.1111/j.1439-0531.2006.00787.x
Source: PubMed

ABSTRACT Signal transducers and activators of transcription (STATs) are a group of proteins involved in signal transduction from numerous bioactive substances. Hormones and cytokines such as leukaemia inhibitory factor, interferon-tau and prolactin, which play key roles during early pregnancy, activate the Janus kinase (JAK)/STAT signalling pathway. The STATs are thus involved in the regulation of implantation, establishing uterine receptivity and regulation of the maternal immune response. It seems that STATs can orchestrate signals from hormones and cytokines in different cell types and may therefore generate numerous biological effects, despite the relatively small number of receptors activating the JAK/STAT pathway. This review summarizes the participation of STATs in the main processes of early pregnancy, especially regarding their pleiotropy and redundancy.

0 Bookmarks
 · 
49 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytokines are involved in almost all processes during the menstrual cycle, the fertilization period and pregnancy. They are expressed in numerous reproduction-related body fluids and tissues. Disorders of cytokine expression patterns may cause pregnancy pathologies. Therefore, cytokines have the potential as new biomarkers in different body compartments for a variety of such pathologies. Furthermore, cytokines may also serve to treat fertility and pregnancy disorders. The IL-6-like family of cytokines is an intensively investigated group of cytokines with well-accepted functions in fertility and pregnancy. This article summarizes current knowledge on IL-6-like cytokines in regard of their role in reproduction and their potential for new strategies in the treatment of reproductive pathologies.
    Expert Review of Clinical Immunology 09/2011; 7(5):603-9. · 2.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary1. Life history theory predicts that immunity should be plastic and reflect environmental contexts. However, individual variation in immune investment may arise not just because of individual adjustment, but because of developmental, physiological, genetic or immunological constraints which lead to non-adaptive responses by limiting or eliminating flexibility in immune investment. Constraints can arise because organisms are single integrated units with interconnected and interacting components, in which physiological and genetic control mechanisms may limit or constrain immunity. We review some of the key underlying genetic and physiological factors that may constrain the occurrence and intensity of immune responses.2. A major part of individual variability may rest on variation in genetic background. Genetic-based constraints can limit or influence immune responses, particularly through pleiotropy and epistatic interactions. In addition, genetic variation, an important driver of variation in antigen recognition and immune system polarization, can be constrained through linkage disequilibrium and genetic drift. Epigenetic changes can also constrain or limit immune responses in future generations based on individual experience.3. The immune system itself can influence individual flexibility in immune investment. Throughout development individuals face tradeoffs within the immune system that favour the expression of one trait at the expense of another. Ontogenetic differences can cause juveniles and adults to produce entirely different immune responses to the same pathogen. T-helper 1 (Th1)/T-helper 1 (Th2) polarization during infection also imposes constraints upon an individual’s immune responsiveness, with the consequence that hosts cannot simultaneously mount strong responses using both Th1 and Th2 cells. In addition, evidence suggests that flexibility in immune responses becomes constrained with age through accumulation of memory cells at the expense of naïve cells, decreased function of cells involved in adaptive and innate immunity, and programming of HPA-immune interactions.4. In summary, selection on a particular immune trait can have effects on other immune components or phenotypic characters, as revealed by artificial selection studies. In particular selection for increased investment in compartments of the immune system leads to decreased investment in other competing life history functions and/or marked changes in other immune components. The role of past experience, even the past experience of parents, may limit and constrain immune responses through influencing the ontogeny of immunity, as well as through epigenetic influences.
    Functional Ecology 01/2011; 25(1):61 - 73. · 4.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via leukemia inhibitory factor- (LIF-) induced activation of signal transducer and activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at its ser727 binding site, possible crosstalk with intracellular MAPK signaling, and their functional implications are the object of the present investigation. JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p-STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per Western blot. Immunocytochemistry confirmed results, but also pinpointed the location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was studied with a colorimetric ELISA-based assay. Cell viability and invasion capability were assessed by MTS and Matrigel assays. Our results demonstrate that LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness are enhanced after LIF stimulation and ERK1/2 blockage. In contrast, proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The findings herein show that blocking ERK1/2 increases LIF-induced STAT3 phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk, which leads to enhanced invasiveness and reduced proliferation.
    The Scientific World Journal 01/2013; 2013:259845. · 1.73 Impact Factor