Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway inflammation by regulating chemokine expression. In a mouse allergic asthma model, we found that mRNA expression of intelectin-2 as well as MCP-1 and -3 in mouse lung was increased very early (within 2 h) after allergen challenge. Expression of intelectin protein was localized to mucous cells in airway epithelium. Treatment of MLE12 mouse lung epithelial cells with interleukin IL-13, a critical mediator of allergic airway disease, induced expression of intelectin-1 and -2 as well as MCP-1 and -3. When IL-13-induced intelectin-1 and -2 expression was inhibited by RNA interference, IL-13-induced extracellular signal-regulated kinase 1/2 phosphorylation and MCP-1 and -3 production by MLE12 cells was inhibited. Furthermore, inhibition of intelectin expression by airway transfection with shRNA targeting intelectin-1 and -2 attenuated allergen-induced airway inflammation. We conclude that intelectin, a molecule expressed by airway epithelial cells and upregulated in asthma, is required for IL-13-induced MCP-1 and -3 production in mouse lung epithelial cells and contributes to allergic airway inflammation.
H₂S prevents vascular restructuring caused by excessive proliferation of smooth muscle cells via apoptosis induction, which helps to maintain normal vascular structures.
Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected. Expressions of key TLR/NO pathway genes (TLR3/4/7/8, NF-κB p65, and iNOS) in cervical epithelial cells were detected by quantitative reverse transcription PCR. Expressions of TLR4, NF-κB p65, and iNOS in CaSki, HeLa, and C33a cells were determined by Western blot. NO concentration in cervical canal of CC group was significantly higher than in other groups (P < 0.05). Positive rates of iNOS in cervical tissues were 72.1%, 28.2%, and 3.1% in the CC group, HR-HPV group, and controls, respectively (P < 0.05). Levels of TLR3, TLR4, TLR7, TLR8, NF-κB p65, and iNOS in cervical epithelial cells were higher in CC group than in other groups (P < 0.05). Both mRNA and protein levels of TLR4, NF-κB p65, and iNOS were higher in HPV-positive HeLa and CaSki cells than in HPV-negative C33a cells (P < 0.05). Together, these results suggest that TLR/NO signaling pathway may be involved in pathogenesis of cervical cancer caused by HR-HPV.
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