Methacycline hydrochloride (Rondomycin) is a broad-spectrum semisynthetic antibiotic related to TETRACYCLINE but excreted more slowly and maintaining effective blood levels for a more extended period.

Methacycline, within pulmonary alveolar macrophages, does not alter the response gene of TGF-β1 nor attenuates the aggregation of inflammatory cells. Following tracheal aspiration of bleomycin, intraperitoneal injection of Methacycline at 100 mg/kg, starting on day 10, enhances survival rates by day 17. Methacycline mitigates bleomycin-induced classical EMT (Epithelial-Mesenchymal Transition) markers, including SNAIL1, TWIST1, type I collagen, fibronectin, and their mRNA expressions.

Methacycline inhibits the TGF-β1-induced non-Smad signaling pathways, including the activation of c-Jun N-terminal kinase (JNK), p38, and Akt, without suppressing Smad or β-catenin transcriptional activities. It does not affect the baseline activities of JNK, p38, or Akt, nor the TGF-β1 response of lung fibroblasts. Additionally, methacycline inhibits the TGF-β1-induced expression of α-smooth muscle actin (α-SMA), SNAIL1, and type I collagen in primary alveolar epithelial cells.