Mechanisms of tissue inhibitor of metalloproteinase 1 augmentation by IL-13 on TGF-beta 1-stimulated primary human fibroblasts.

Background: TGF-beta induces expression of tissue inhibitor of metalloproteinase 1 (TIMP-1), a potent inhibitor of matrix metalloproteinases that controls extracellular matrix metabolism and deposition. IL-13 alone does not induce TIMP-1, but in combination with TGF-beta it augments TIMP-1 expression. Although these interactions have implications for remodeling in asthma, little is understood regarding the mechanisms controlling TIMP-1 product.

Defective apoptotic cell phagocytosis attenuates prostaglandin E2 and 15-hydroxyeicosatetraenoic acid in severe asthma alveolar macrophages.

Rationale: Clearance of apoptotic cells is crucial to the resolution of inflammation and development of fibrosis, but the process is not well understood in normal or diseased human lungs.

Objectives: To determine phagocytosis of apoptotic cells by primary human alveolar macrophages and whether defects in uptake of apoptotic cells are associated with decreases in antiinflammatory/antifibrotic mediators.

Methods: Human bronchoalveolar lavage macrophages (AMphis) from normal control subjects and subjects with mild-moderate or severe asthma were examined in vitro for phagocytosis of apoptotic human T-cell line Jurkats and secretion of inflammatory mediators.

Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis, a disease caused by Mycobacterium tuberculosis strains that are resistant at least to rifampin and isoniazid, entails extended treatment, expensive and toxic regimens, and higher rates of treatment failure and death. We retrospectively analyzed the outcomes in 205 patients treated at our center for multidrug-resistant tuberculosis, with strains resistant to a median of six drugs, and compared the results with those of our previous series. Logistic regression and survival analysis were used to evaluate short- and long-term outcomes, respectively.

Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation.

Ingestion of apoptotic cells in vitro by macrophages induces TGF-beta1 secretion, resulting in an anti-inflammatory effect and suppression of proinflammatory mediators. Here, we show in vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation. This enhancement appeared to require phosphatidylserine (PS) on the apoptotic cells and local induction of TGF-beta1.