Inhibitory Effect of P22077 on Airway Inflammation in Rats with COPD and Its Mechanism.

Purpose: Here, we studied the pharmacological effect of P22077 on airway inflammation induced by lipopolysaccharide and cigarette smoke and explored the therapeutic mechanism of P22077 in COPD model RAT. Patients and Methods: The COPD model was established by lipopolysaccharide combined with fumigation; animals were treated with vehicle or P22077. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for analysis. Results: Our results showed that P22077 treatment significantly improved the airway inflammation of COPD model RAT and reduced the recruitment of leukocytes in BALF, and hypersecretion of interleukin-18 (IL-18), interleukin-1ß (IL-1ß) in BALF and serum. H&E staining showed that P22077 treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. PAS staining showed that The proliferation of cup cells in the airway wall and the number of bronchial cup cells were significantly reduced in rats treated with P22077. In addition, we found that P22077 treatment suppressed the generation of the NLRP3/ASC/Caspase 1 inflammasome complex to inhibit the inflammatory response caused by IL-1ß and IL-18. Conclusion: Conclusion: P22077 inhibits expression of NLRP3 pathway-related inflammatory factors and proteins and reduces the airway inflammatory response and inflammatory cell aggregation in COPD rats. The underlying mechanism may be related to the down-regulation of NLRP3 inflammatory vesicle signaling pathway expression.

Arabidopsis ERD15 regulated by BBX24 plays a positive role in UV-B signaling.

Ultraviolet-B (UV-B, 280-315 nm) is a minor component of solar radiation, but it has a major regulatory impact on plant growth and development. Solar UV-B regulates numerous aspects of plant metabolism, morphology and physiology through altering the expression of hundreds of genes. EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15) is a drought-induced rapid response gene, formerly known as a negative regulator of the abscisic acid (ABA) signaling pathway. It is unclear whether ERD15 is involved in UV-B-induced photomorphogenesis. Previously, we reported that the BBX24 transcriptional factor negatively regulated UV-B signaling. In the present study, we identified that ERD15 is involved in UV-B photomorphogenesis as a positive regulator at phenotypic, physiological and molecular levels. Our results indicated that ERD15 expression is suppressed by UV-B, inhibited the elongation of Arabidopsis hypocotyls in a UV-B-dependent manner, promoted the expression of related UV-B signaling genes and increased the total antioxidant capacity of Arabidopsis under UV-B. Genetic hybridization results show that ERD15 acts downstream of BBX24, and BBX24 protein mediated the expression of ERD15 by binding to its promoter. Thus, ERD15 is a novel positive regulator of the UV-B signaling pathway, which is downstream of BBX24 and regulated by BBX24 protein to participate in UV-B photomorphogenesis.

BBX24 Interacts with DELLA to Regulate UV-B-Induced Photomorphogenesis in Arabidopsis thaliana.

UV-B radiation, sensed by the photoreceptor UVR8, induces signal transduction for plant photomorphogenesis. UV-B radiation affects the concentration of the endogenous plant hormone gibberellin (GA), which in turn triggers DELLA protein degradation through the 26S proteasome pathway. DELLA is a negative regulator in GA signaling, partially relieving the inhibition of hypocotyl growth induced by UV-B in Arabidopsis thaliana. However, GAs do usually not work independently but integrate in complex networks linking to other plant hormones and responses to external environmental signals. Until now, our understanding of the regulatory network underlying GA-involved UV-B photomorphogenesis had remained elusive. In the present research, we investigate the crosstalk between the GA and UV-B signaling pathways in UV-B-induced photomorphogenesis of Arabidopsis thaliana. Compared with wild type Landsberg erecta (Ler), the abundance of HY5, CHS, FLS, and UF3GT were found to be down-regulated in rga-24 and gai-t6 mutants under UV-B radiation, indicating that DELLA is a positive regulator in UV-B-induced photomorphogenesis. Our results indicate that BBX24 interacts with RGA (one of the functional DELLA family members). Furthermore, we also found that RGA interacts with HY5 (the master regulator in plant photomorphogenesis). Collectively, our findings suggest that the HY5−BBX24−DELLA module serves as an important signal regulating network, in which GA is involved in UV-B signaling to regulate hypocotyl inhibition.

Gibberellin regulates UV-B-induced hypocotyl growth inhibition in Arabidopsis thaliana.

Plant response to light is a complex and diverse phenomenon. Several studies have elucidated the mechanisms via which light and hormones regulate hypocotyl growth. However, the hormone-dependent ultraviolet-B (UV-B) response in plants remains obscure. Involvement of gibberellins (GAs) in UV-B-induced hypocotyl inhibition and its mechanisms in Arabidopsis thaliana were investigated in the present research. UV-B exposure remarkably decreased the endogenous GA3 content through the UV RESISTANCE LOCUS 8 (UVR8) receptor pathway, and exogenous GA3 partially restored the hypocotyl growth. UV-B irradiation affected the expression levels of GA metabolism-related genes (GA20ox1, GA2ox1 and GA3ox1) in the hy5-215 mutant, resulting in increased GA content.ELONGATED HYPOCOTYL 5 (HY5) promoted the accumulation of DELLA proteins under UV-B radiation; HY5 appeared to regulate the abundance of DELLAs at the transcriptional level under UV-B. As a result, the GA3 content decreased, which eventually led to the shortening of the hypocotyl. To conclude, the present study provides new insight into the regulation of plant photomorphogenesis under UV-B.