Publications by authors named "Karosham D Reddy"

4 Publications

  • Page 1 of 1

Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment .

ERJ Open Res 2021 Apr 31;7(2). Epub 2021 May 31.

Airway Physiology and Imaging Group, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia.

https://bit.ly/3muvNsW.
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http://dx.doi.org/10.1183/23120541.00117-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165371PMC
April 2021

Current-Smoking alters Gene Expression and DNA Methylation in the Nasal Epithelium of Asthmatics.

Am J Respir Cell Mol Biol 2021 May 14. Epub 2021 May 14.

University of Technology Sydney, 1994, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, Sydney, New South Wales, Australia.

Current-smoking contributes to worsened asthma prognosis, more severe symptoms and limits the beneficial effects of corticosteroids. As the nasal epithelium can reflect smoking-induced changes in the lower airways, it is a relevant source to investigate changes in gene expression and DNA methylation. This study explores gene expression and DNA methylation changes in current and ex-smokers with asthma. Matched gene expression and epigenome-wide DNA methylation samples collected from nasal brushings of 55 patients enrolled in a clinical trial investigation of current and ex-smoker asthma patients were analysed. Differential gene expression and DNA methylation analyses were conducted comparing current- vs ex-smokers. Expression quantitative trait methylation (eQTM) analysis was completed to explore smoking relevant genes by CpG sites that differ between current and ex-smokers. To investigate the relevance of the smoking-associated DNA methylation changes for the lower airways, significant CpG sites were explored in bronchial biopsies from patients who had stopped smoking. 809 genes and 18,814 CpG sites were differentially associated with current-smoking in the nose. The cis-eQTM analysis uncovered 171 CpG sites whose methylation status associated with smoking-related gene expression, including AHRR, ALDH3A1, CYP1A1 and CYP1B1. Methylation status of CpG sites altered by current-smoking reversed with one-year smoking cessation. We confirm current-smoking alters epigenetic patterns and affects gene expression in the nasal epithelium of asthma patients, which is partially reversible in bronhcial biopsies after smoking cessation. We demonstrate the ability to discern molecular changes in the nasal epithelium, presenting this as a tool in future investigations into disease-relevant effects of tobacco smoke.
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http://dx.doi.org/10.1165/rcmb.2020-0553OCDOI Listing
May 2021

Sex-specific effects of in utero and adult tobacco smoke exposure.

Am J Physiol Lung Cell Mol Physiol 2021 01 21;320(1):L63-L72. Epub 2020 Oct 21.

School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.

Tobacco smoke has harmful effects on a multiorgan level. Exposure to smoke, whether in utero or environmental, significantly increases susceptibility. This susceptibility has been identified to be divergent between males and females. However, there remains a distinct lack of thorough research into the relationship between sex and exposure to tobacco. Females tend to generate a more significant response than males during adulthood exposure. The intrauterine environment is meticulously controlled, and exposure to tobacco presents a significant factor that contributes to poor health outcomes and susceptibility later in life. Analysis of these effects in relation to the sex of the offspring is yet to be holistically reviewed and summarized. In this review, we will delineate the time-dependent relationship between tobacco smoke exposure and sex-specific disease susceptibility. We further outline possible biological mechanisms that may contribute to the identified pattern.
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http://dx.doi.org/10.1152/ajplung.00273.2020DOI Listing
January 2021

Sexually dimorphic production of interleukin-6 in respiratory disease.

Physiol Rep 2020 06;8(11):e14459

School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia.

Diverging susceptibility and severity in respiratory diseases is prevalent between males and females. Sex hormones have inconclusively been attributed as the cause of these differences, however, strong evidence exists promoting genetic factors leading to sexual dimorphism. As such, we investigate differential proinflammatory cytokine (interleukin (IL)-6 and CXCL8) release from TNF-α stimulated primary human lung fibroblasts in vitro. We present, for the first time, in vitro evidence supporting clinical findings of differential production of IL-6 between males and females across various respiratory diseases. IL-6 was found to be produced approximately two times more from fibroblasts derived from females compared to males. As such we demonstrate sexual dimorphism in cytokine production of IL-6 outside the context of biological factors in the human body. As such, our data highlight that differences exist between males and females in the absence of sex hormones. We, for the first time, demonstrate inherent in vitro differences exist between males and females in pulmonary fibroblasts.
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http://dx.doi.org/10.14814/phy2.14459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260763PMC
June 2020