## 4 Discussion  
The present study demonstrated that the BALF and lung parenchyma of mice experienced inflammatory cell infiltration as a result of exposure to CS and LPS. The influx of lymphocytes and macrophages was accompanied by increased concentrations of IL-6 and TNF-\(\alpha\). Treatment with CBD, however, attenuated these effects of CS and LPS. CBD was  
Figure 6: NF-kB and MAPK activity in lung tissues resulting from CBD effects. Western blotting showing the levels of phosphorylation of ERK, p38 MAPK, and NF-kB in lung tissues. Control: mice instilled intratracheally with normal saline; COPD; mice exposed to CS and LPS; RO mice exposed to 10 mg/kg rofumlast plus CS and LPS; CBD 100. mice exposed to 100 mg/kg CBD plus CS and LPS; CBD 200. mice exposed to 200 mg/kg CBD plus CS and LPS. Results are presented as means \(\pm\) SEMs. **\(p\) < 0.01 compared with the control group; * \(p\) < 0.05, **\(p\) < 0.01 compared with the COPD group. found to exert its anti-inflammatory effects in this mouse model of COPD by preventing the phosphorylation and activation of NF-\(\kappa\)B and MAPKs, by reducing the production of the proinflammatory mediators IL-1\(\beta\), IL-6, TNF-\(\alpha\), and MCP-1, and by attenuating the expression of the fibrosis inducers TGF-\(\beta\), \(\alpha\)-SMA, MMP-7, MMP-9, and TIMP-1. COPD is predominantly caused by cigarette smoking and is defined by pulmonary inflammation, including increases in cells of both the innate and adaptive immune systems. LPS present in CS is a substance that forms the cell membrane of Gram-negative bacteria and causes pulmonary and systemic inflammation in humans [27]. The present study established a COPD model in mice, induced by exposure to CS for 8 weeks and exposure every other week to intranasal LPS. The pathological changes resulting from exposure to CS and LPS were comparable to the clinical aspects observed in patients with COPD [28]. CBD administered by oral gavage to these mice for 4 weeks, 1 h before exposure to CS, was found to be effective in reducing the manifestations of COPD in this model. The ability of CBD to ameliorate pathological changes in the lungs of CS- and LPS-exposed mice suggests that CBD may be a potent anti-inflammatory agent that inhibits the accumulation of inflammatory cells caused by CS and LPS exposure. The present study demonstrated that mice exposed to CS and LPS had higher amounts of IL-6 and TNF-\(\alpha\) in their BALF and lung tissue, whereas CBD-treated mice had much lower levels of these cytokines. Increased BALF IL-6, IL-8, and TNF-\(\alpha\) levels in COPD patients are used as indicators of the systemic inflammatory response, and their levels are associated with the severity of the disease [29]. The finding that CBD downregulated the production of proinflammatory cytokines during lung inflammation suggests that CBD therapy may affect downstream processes, such as the inflow of inflammatory cells and the amounts of mediators that exacerbate the inflammatory response. Additionally, the expression of \(\alpha\)-SMA, TGF-\(\beta\), MMPs, and TIMPs was significantly decreased by CBD. Large levels of TGF-\(\beta\) are created during the onset and maintenance of pulmonary fibrosis, which can lead to additional nearby fibrosis. MCP-1, a recognized inducer of TGF-\(\beta\), maintains the fibrotic process through the direct control of TGF-\(\beta\) and possibly the ensuing accumulation of myofibbacks as well [30]. MCP-1 regulation of inflammation may be crucial in the fibrotic response. One of the most important indicators of fibrosis is the protein \(\alpha\)-SMA, which TGF-\(\beta\) upregulates [31]. TGF-\(\beta\) enhanced \(\alpha\)-SMA expression, along with a decrease in E-cadherin expression, in a dose- and time-dependent manner [32]. These changes result in the secretion of excess collagen-I, leading to pulmonary fibrosis [33]. The expression of \(\alpha\)-SMA was shown to be involved in interleukin-1\(\beta\) (IL-1\(\beta\))-regulated inflammation in rat lung myofibroblasts [34].