calpain and Pneumonia

Exposure to cigarette smoke including secondhand smoking is the most important risk factor in the development of chronic obstructive pulmonary disease where incidence has substantially increased in recent decades. The mechanisms responsible for cigarette smoke-induced pulmonary inflammation remain unclear, and thus lack of effective treatment. The present study investigated the effect of calpeptin on attenuating cigarette smoke induced pulmonary inflammation and its potential mechanism and function. When BALB/c mice were exposed to cigarette smoke and received calpeptin intraperitoneally injection after 90 days, calpeptin histologically attenuated the accumulation of neutrophils (P < 0.001), eosinophils (P < 0.001), macrophages (P < 0.01), fibrinous exudation and proliferation within the interstitial and alveolar spaces. BEAS-2B cells were added with cigarette smoke extract in vitro and treated with calpeptin for 24 h in the treatment group. The markedly upregulation of μ-calpain (P < 0.01), m-calpain (P < 0.001) and IκBα (P < 0.01) in cigarette smoke-induced lungs were simultaneously decreased by calpeptin treatment (P < 0.05). The increased expression of μ-calpain, m-calpain and IκBα (P < 0.05) in cigarette smoke extract-stimulated BEAS-2B cells were also decreased by calpeptin treatment (P < 0.05). These data indicated that calpeptin attenuated cigarette smoke-induced pulmonary inflammation by suppressing the pathway of μ-calpain, m-calpain and IκBα in vivo and in vitro. Calpeptin might have a potential for prevention of the development of inflammatory pulmonary diseases and warrant further pharmaceutical investigation.

Topics: Animals; Calpain; Cell Line; Dipeptides; Humans; Male; Mice; Mice, Inbred BALB C; NF-KappaB Inhibitor alpha; Pneumonia; Signal Transduction; Tobacco Smoke Pollution

Lobar pneumonia, one of the community-acquired pneumonia (CAP), is a common pediatric low respiratory tract infection. Calpains are Ca

Topics: Apoptosis; Calpain; Cell Proliferation; Child; Child, Preschool; Cytokines; Female; Humans; Immunologic Factors; Infant; Infant, Newborn; Lung; Male; Models, Biological; Pneumonia

Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists.

Topics: Acids; Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Bacterial Toxins; Calpain; Coinfection; Enzyme Activation; Hemolysin Proteins; Humans; Killer Cells, Natural; Lysosomes; Macrophages, Alveolar; Mice; Microbial Viability; Models, Biological; Neutrophils; Opportunistic Infections; Pneumonia; Pseudomonas aeruginosa; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus