American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2014
Aging Mesenchymal Stem Cells Fail to Protect due to Impaired Migration and Anti-Inflammatory Response.
Aging is characterized by functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. With age, there is an increase in the incidence and severity of chronic and acute lung diseases. However, the relationship between age and the lung's reduced ability to repair is far from established and necessitates further research in the field. ⋯ Taken together, the decreased expression of cytokine and chemokine receptors in aged B-MSCs compromises their protective role by perturbing the potential of B-MSCs to become activated and mobilize to the site of injury.
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Am. J. Respir. Crit. Care Med. · Apr 2014
Transforming Growth Factor β-induced Protein Promotes Severe Vascular Inflammatory Responses.
Sepsis is a systemic inflammatory condition resulting from bacterial infections; it has a high mortality rate and limited therapeutic options. Despite extensive research into the mechanisms driving bacterial sepsis, the target molecules controlling vascular leakage are still largely unknown. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins. ⋯ Collectively, our findings demonstrate that the TGFBIp-αvβ5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.
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Am. J. Respir. Crit. Care Med. · Apr 2014
Pseudomonas aeruginosa Type-3 secretion system dampens host defense by exploiting the NLRC4-coupled inflammasome.
Pseudomonas aeruginosa, a major problem pathogen responsible for severe infections in critically ill patients, triggers, through a functional type-3 secretion system (T3SS), the activation of an intracellular cytosolic sensor of innate immunity, NLRC4. Although the NLRC4-inflammasome-dependent response contributes to increased clearance of intracellular pathogens, it seems that NLRC4 inflammasome activation decreases the clearance of P. aeruginosa, a mainly extracellular pathogen. ⋯ We report a new role of the T3SS apparatus itself, independently of exotoxin translocation. Through NLRC4 inflammasome activation, the T3SS promotes IL-18 secretion, which dampens a beneficial IL-17-mediated antimicrobial host response.