| 1 | Med. Hypotheses 2006 -1 66: 286-93 |
|---|---|
| PMID | 16183209 |
| Title | The role of HLA-G in cytokine homeostasis during early pregnancy complicated with maternal infections: a novel etiopathological approach to the neurodevelopmental understanding of schizophrenia. |
| Abstract | schizophreniais perhaps the most enigmatic and tragic psychotic disorder with remarkable mortality and morbidity.schizophreniais complex and clinically a heterogeneous disorder. The etiological basis ofschizophrenia范围从neurodevelopmenta自身免疫性l hypothesis in one hand and involvement of different major gene segment with susceptibility loci on the other. Recently, neurodevelopmental hypothesis gained much impetus over the other domain. To support the neurodevelopmental basis, a number of investigations have shown that maternal infections during pregnancy increases the risk of the offspring developingschizophreniaand other neurodevelopmental disorders. The pathological mechanisms underlying this phenomenon is largely unknown. Many have suggested the involvement of different immune markers and shown that cytokines generated in response to maternal infection alter early brain development through their inflammatory activity. However, these findings have escaped discussion on various important issues related to cytokine homeostasis which depends on a large number of immune parameters including non-classicalHLA-Gmolecules. Infections during early stages of pregnancy may alter cytokine regulation by disturbing the whole uterine immune milieu. To elucidate this issue, authors have tried to correlate the possible relationships between maternal infections and aberration of immune networking at the feto-maternal interface and their subsequent influence on the structural and functional abnormalities of the developing brain. The authors hypothesize that there exists a counter regulatory interaction among proinflammatory cytokines like TNF-alpha,HLA-Gmolecules and different immune cells like NK cells. We emphasize thatHLA-Gmolecules are the novel immune players which maintain the immune homeostasis during early pregnancy in a manner that it can protect developing fetus from maternal immune attack. However, maternal infections may lead to the disturbance ofHLA-Gexpression which in turn may fail to maintain its otherwise inhibitory potential to down regulate the detrimental inflammatory cytokines. Investigation on such interaction may unravel novel molecular mechanisms of neurodevelopmental basis ofschizophrenia. Testing of our proposed hypothesis on animal models and on in vitro derived extravillous trophoblast cell lines holds promise of great insights to usher a new dimension ofschizophreniaresearch and for developing new therapeutic strategies for better treatment and to adopt genetic prediction inschizophreniamanagement paradigm. |
| SCZ Keywords | schizophrenia |
| 2 | Am. J. Reprod. Immunol. 2009 Sep 62: 139-46 |
| PMID | 19694639 |
| Title | H3N2 influenza A virus replicates in immortalized human first trimester trophoblast cell lines and induces their rapid apoptosis. |
| Abstract | Epidemiological data suggested that pandemic influenza increased the risks of spontaneous abortion and premature labor, while seasonal influenza also increased the risk ofschizophreniain adolescence. However, their pathogenesis is so far unknown. The first trimester trophoblast cell lines, namely, Swan71 and HTR8 cells were challenged with A/Udorn/72 influenza virus (H3N2). At indicated time points, cells were examined for expression of influenza proteins. Viral replication in culture media, apoptosis and the expression of human leukocyte antigen (HLA)-G were also examined. Intracellular localization of viral proteins was observed. Twenty-four hours after inoculation, virus was detected in culture media while most cells fell into apoptosis. During apoptosis, expression ofHLA-Gwas unchanged. We revealed replication of low pathogenic influenza virus in the first trimester trophoblast cell lines. Placental damages are likely to be induced by direct cytopathic effects of influenza virus and subsequent apoptosis rather than down regulation ofHLA-Gexpression and subsequent rejection by maternal immune system. |
| SCZ Keywords | schizophrenia |