Respiratory Research最新文献

Background: Inflammation drives COPD development in people living with HIV (PLwHIV), and the HIV virus impairs T regulatory (Treg) cell responses that deter immune-mediated lung injury. This study sought to determine how cigarette smoke exposure alters lung Treg responses to increase COPD susceptibility in PLwHIV.

Methods: Lung lavage levels of the Treg chemoattractant CXCL11 were quantified in a cohort of 26 HIV-infected subjects and 34 age-matched controls. To ascertain how CXCL11 modifies lung Treg responses, analyses were then conducted using a chimeric HIV (EcoHIV) infection smoke exposure mouse model and elastase treatment of Treg depleted (DEREG) mice.

Results: CXCL11 lung lavage levels increased in HIV + subjects compared to controls. However, CXCL11 levels were significantly lower in those HIV + subjects with a reduced diffusing capacity for carbon monoxide compared to HIV + subjects with normal lung function. Cigarette smoke exposure reduced CXCL11 levels in HIV + current smokers and decreased lung Cxcl11 levels and Treg frequency in control and EcoHIV-infected mice. Cigarette smoke increased lung c-Src activity in mice and the c-Src inhibitor AZD0530 restored Cxcl11 expression in smoke exposed mice and alveolar macrophages. Direct administration of CXCL11 protein to the airways of EcoHIV infected or smoke exposed mice significantly enhanced lung Treg responses. Treg deficient DEREG mice exhibited increased airway resistance at baseline and had greater lung tissue destruction post elastase treatment.

Conclusions: These findings indicate that cigarette smoke activates c-Src to suppress CXCL11 levels thereby diminishing lung Treg responses that counter airways disease and lung tissue destruction in HIV-infected individuals.

Background: People with HIV (PWH) are at increased risk for chronic lung disease and may be more susceptible to pulmonary complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It remains unclear whether HIV infection modifies long-term pulmonary outcomes after coronavirus disease 2019 (COVID-19). This study assessed longitudinal changes in pulmonary function and respiratory symptoms among PWH and people without HIV (PWoH) with serologically-confirmed SARS-CoV-2 infection.

Methods: We analyzed data from the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS), a prospective US cohort of PWH and PWoH. Participants with serologic evidence of past SARS-CoV-2 infection and acceptable pre- and post-SARS-CoV-2 pulmonary function testing (PFT) including spirometry and diffusing capacity for carbon monoxide (DLCO) were included. Annualized changes in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and DLCO were compared by HIV serostatus, stratified by sex. Respiratory symptoms were assessed using the St. George's Respiratory Questionnaire (SGRQ). Linear regression estimated differences in pulmonary function change by HIV serostatus, stratifying by relevant covariates.

Results: Among 778 participants (204 men; 574 women) exposed to SARS-CoV-2 and who underwent PFTs before and after infection, 66% were PWH. Men with HIV (MWH) had a mean annualized FEV₁ decline of -44.3 mL/year versus -33.8 mL/year in men without HIV (MWoH) (mean difference -10.5 mL/year; 95% CI: -30.7, 9.7). Among women, FEV₁ declined -19.8 mL/year in PWH vs. -14.8 mL/year in PWoH (mean difference -5.0 mL/year; 95% CI: -18.2, 8.2). Changes in FVC and DLCO were similar across HIV serostatus groups. No consistent differences in respiratory symptom changes were observed between PWH and PWoH. Subgroup analyses did not reveal any HIV-associated differential changes.

Conclusions: Among individuals with serologic evidence of SARS-CoV-2 infection, HIV serostatus was not associated with greater declines in pulmonary function or worsening of respiratory symptoms. Our findings suggest that having HIV alone may not increase the risk for pulmonary impairments following a SARS-CoV-2 infection. Further research is needed to understand how uncontrolled HIV infection and severity of SARS-CoV-2 infection may increase risks of adverse pulmonary outcomes following a SARS-CoV-2 infection.

Objective: This study aimed to combine network pharmacology with in vitro experiments to identify the key targets and potential mechanisms of salidroside (Sal) in the treatment of acute lung injury (ALI).

Methods: Potential targets related to Sal and ALI were retrieved from the ChEMBL, SuperPRED, SwissTargetPrediction, GeneCards, OMIM, and CTD databases. Overlapping targets were imported into the STRING database and Cytoscape software to construct a protein-protein interaction (PPI) network and identify core targets. Functional enrichment analysis of these core genes, including GO and KEGG pathways, was performed using the DAVID database. Two genes, MAPK14 and GPX4, directly relevant to subsequent validation, were selected for molecular docking analysis. Furthermore, an in vitro model of ALI was established using LPS-induced alveolar type II epithelial cells to verify the protective mechanism of Sal.

Results: A total of 355 potential targets associated with Sal in ALI treatment were identified. In vitro experiments showed that, compared to the LPS group, the Sal group exhibited significantly reduced secretion of IL-6, ROS, p-MAPK, MDA, and Fe²⁺, along with increased GPX4 expression and attenuated lung injury.

Conclusion: Integrated network pharmacology and experimental validation suggest that Sal pretreatment alleviates inflammatory response and oxidative stress, likely through regulation of the MAPK/GPX4 signaling pathway, thereby providing protection against lung tissue injury.