**2. Inhalation of some agents cause activation of the NF-κB inflammatory pathway in the lung**

#### **Asbestos**

Asbestos belongs to a group of physically occurring, hydrated mineral silicate fibers that are causally related to the progression of pulmonary diseases [88]. Iron, which exists in asbestos fibers, cause cellular redox changes by generation of intracellular reactive oxygen species, leading to activation of NF-κB. It has been shown that, after inhalation of crocidolite and chrysotile asbestos, nuclear translocation of RelA increases in rat airway epithelial cells (Table 1). The main reason is that macrophages phagocytize asbestos but cannot ''digest'' these fibers. Because the asbestos harms them, these macrophages secret TNF-α, and this cytokine mediates activation of NF-κB [73, 89-92].

task of this macrolide. Suppression of NF-κB activity reveals other proinflammatory molecules regulated by this factor as an AZM effect relevant to the treatment of CF [87].

Acute respiratory distress syndrome (ARDS) is known for enormous infiltration of neutrophils into the lungs accompanied by leak of serum proteins, especially albumin, into the alveolar space, blood loss in the intra-alveolar space, and interstitial edema, all important and frequent signs in exacerbation of ARDS. In spite of the occurrence of ARDS in all over the world, the precise pathophysiology mechanisms remain to be detailed [88].

Varying expression levels of proinflammatory cytokines are associated with the progression of ARDS. overexperssion of proinflammatory cytokines such as TNF-α, IL-6 and IL-8 in the lung has been demontrated in bronchoalveolar lavage (BAL) of ARDS patients and is

Patients with proved ARDS revealed increased activation of NF-κB in alveolar macrophages, in comparison with control subjects without acute lung injury [73]. Because there were no notable increases in the levels of transcription factors, including CREB, AP-I , or SP- I activation, in alveolar macrophages from patients with ARDS, NF-κB is suggested to be a significant upstream regulator for cytokine gene expression in ARDS patients, because of its existence on the enhancer of proinflammatory cytokines (Table 1). The level of subunits p50, p65, and c- Rel decreased in cytoplasm of alveolar macrophages in ARDS subjects, proving the existence of an ongoing stimulus for NF-κB activation. Increased levels of oxygen radicals, proinflarnmatory cytokines, and endotoxin in ARDS might be associated

with NF-κB activation. TNF-a and IL-8 are increased in BAL of ARDS subjects [88].

**2. Inhalation of some agents cause activation of the NF-κB inflammatory** 

Asbestos belongs to a group of physically occurring, hydrated mineral silicate fibers that are causally related to the progression of pulmonary diseases [88]. Iron, which exists in asbestos fibers, cause cellular redox changes by generation of intracellular reactive oxygen species, leading to activation of NF-κB. It has been shown that, after inhalation of crocidolite and chrysotile asbestos, nuclear translocation of RelA increases in rat airway epithelial cells (Table 1). The main reason is that macrophages phagocytize asbestos but cannot ''digest'' these fibers. Because the asbestos harms them, these macrophages secret TNF-α, and this

NF-κB activation can alsobe caused by oxygen radicals. Our in vivo data from a hemorrhage-induced murine model of ARDS indicates an outstanding role for xanthine oxidase, a kind of oxygen radical, in stimulation of NF-κB in lung cells [88]. Cytoplasmic and nuclear levels of IκBa are not notibly dissimilar in alveolar macrophages from ARDS subjects and controls, so these findings are rather unexpected, because signals that cause activation of NF-κB would be expected to generate phosphorylation. Alveolar macrophages have a significant protective role in mediating NF-κB activation in the lung and in initiation

**1.5 Acute respiratory distress syndrome** 

correlated with poor outcome [88].

of neutrophilic inflammation [73, 88].

cytokine mediates activation of NF-κB [73, 89-92].

**pathway in the lung** 

**Asbestos** 


Table 1. The implication of NF-κB in inflamatory lung disease.
