Dataset Information

A Study on the Impact of Genetic Polymorphisms of Cytokines TNFα, IFNγ and IL10 in South Indian Leprosy Patients.

ABSTRACT:

Background

Leprosy (Hansen's disease) is a chronic, debilitating disease predominantly of the peripheral nervous system characterized by the impairment of peripheral nerves and subsequent sensory loss caused by Mycobacterium leprae. The pro- and antiinflammatory cytokine genes play a major role in nerve damage in leprosy.

Aims and objectives

The objective of the present study is to ascertain the association of cytokine gene polymorphisms TNFα - 308G/A (rs 1800629), IFNγ +874A/T (rs 2430561), and IL10 - 1082G/A rs 1800896 in causation with leprosy.

Materials and methods

The present study comprised 365 leprosy patients and 185 control subjects. The polymorphisms in TNFα-308, IFNγ+874, and IL10-1082 genes were typed using the amplification refractory mutation system polymerase chain reaction method (ARMS PCR).

Results

The present study found significant association between IL10-1082 GA heterozygote (P < 0.02) and IFNγ+874 AA (P < 0.001) genotype and leprosy. TNFα-308GA could not establish any association with the disease.

Conclusion

The identification of genetic variations in pro- and antiinflammatory cytokines that are susceptible to leprosy would assist in better understanding of the pathogenesis of leprosy and perhaps lead to new approaches for diagnosis and treatment.

SUBMITTER: Kolla VK

PROVIDER: S-EPMC8208288 | biostudies-literature | 2021 Mar-Apr

REPOSITORIES: biostudies-literature

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Publications

A Study on the Impact of Genetic Polymorphisms of Cytokines TNFα, IFNγ and IL10 in South Indian Leprosy Patients.

Kolla Venkata Karunakar VK Sultana Shehnaz S Davala Samuel Abraham Joshi SAJ Valluri Vijaya Lakshmi VL

Indian journal of dermatology 20210301 2

<h4>Background</h4>Leprosy (Hansen's disease) is a chronic, debilitating disease predominantly of the peripheral nervous system characterized by the impairment of peripheral nerves and subsequent sensory loss caused by <i>Mycobacterium leprae</i>. The pro- and antiinflammatory cytokine genes play a major role in nerve damage in leprosy.<h4>Aims and objectives</h4>The objective of the present study is to ascertain the association of cytokine gene polymorphisms TNFα - 308G/A (rs 1800629), IFNγ +87 ...[more]

PMID: 34188268

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Project description:Microglia respond to CNS injuries and diseases with complex reactions, often called "activation." A pro-inflammatory phenotype (also called classical or M1 activation) lies at one extreme of the reactivity spectrum. There were several motivations for this study. First, bacterial endotoxin (lipopolysaccharide, LPS) is the most commonly used pro-inflammatory stimulus for microglia, both in vitro and in vivo; however, pro-inflammatory cytokines (e.g., IFNγ, TNFα) rather than LPS will be encountered with sterile CNS damage and disease. We lack direct comparisons of responses between LPS and such cytokines. Second, while transcriptional profiling is providing substantial data on microglial responses to LPS, these studies mainly use mouse cells and models, and there is increasing evidence that responses of rat microglia can differ. Third, the cytokine milieu is dynamic after acute CNS damage, and an important question in microglial biology is: How malleable are their responses? There are very few studies of effects of resolving cytokines, particularly for rat microglia, and much of the work has focused on pro-inflammatory outcomes. Here, we first exposed primary rat microglia to LPS or to IFNγ+TNFα (I+T) and compared hallmark functional (nitric oxide production, migration) and molecular responses (almost 100 genes), including surface receptors that can be considered part of the sensome. Protein changes for exemplary molecules were also quantified: ARG1, CD206/MRC1, COX-2, iNOS, and PYK2. Despite some similarities, there were notable differences in responses to LPS and I+T. For instance, LPS often evoked higher pro-inflammatory gene expression and also increased several anti-inflammatory genes. Second, we compared the ability of two anti-inflammatory, resolving cytokines (IL-4, IL-10), to counteract responses to LPS and I+T. IL-4 was more effective after I+T than after LPS, and IL-10 was surprisingly ineffective after either stimulus. These results should prove useful in modeling microglial reactivity in vitro; and comparing transcriptional responses to sterile CNS inflammation in vivo.

Dataset Information

A Study on the Impact of Genetic Polymorphisms of Cytokines TNFα, IFNγ and IL10 in South Indian Leprosy Patients.

Background

Aims and objectives

Materials and methods

Results

Conclusion

Publications

A Study on the Impact of Genetic Polymorphisms of Cytokines TNFα, IFNγ and IL10 in South Indian Leprosy Patients.

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