Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice

Background

Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure.

Methods

Mice were exposed to cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL-1α-deficient mice, as well as anti-IL-1α and anti-IL-1β blocking antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell accumulation and activation.

Results

Acute and chronic cigarette smoke exposure led to increased frequency of lung dendritic cells. Accumulation and activation of dendritic cells was IL-1R1/IL-1α dependent, but TLR4- and IL-1β-independent. Corroborating the cellular data, expression of CCL20, a potent dendritic cells chemoattractant, was IL-1R1/IL-1α-dependent. Studies using IL-1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung structural cells for CCL20 expression. Consistent with the importance of dendritic cells in T cell activation, we observed decreased CD4⁺ and CD8⁺ T cell activation in cigarette smoke-exposed IL-1R1-deficient mice.

Conclusion

Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure.     

Phytochemical analysis and evaluation of antioxidant and anti-acetylcholinesterase activities of Euphorbia dendroides L. (Euphorbiaceae) latex

The aim of this study was to evaluate the antioxidant and anti-acetylcholinesterase properties and phytochemical constituents of the latex from Euphorbia dendroides L. (Euphorbiaceae) growing wild in Sicily. Phytochemical analysis revealed that into E. dendroides latex the triterpenoids were the most abundant among the identified compounds. Furthermore, a high content of polyphenols mainly as phenolic acids, was found. The antioxidant and free-radical scavenging properties, by several in vitro assays such as DPPH, TEAC and FRAP, have been evaluated. The results showed that E. dendroides latex has significant antioxidant activity, as measured by DPPH assay (2927.01?±?98.03 µmols of Trolox equivalent (TE)/100g FW). Reactivity towards ABTS radical cation and ferric-reducing antioxidant power (FRAP) values were 7580.95?±?97.65 µmols of TE/100g FW and 4383.13?±?95.30?μmol of TE/100g FW, respectively. The latex exhibited also significant inhibition of acetylcholinesterase activity with an IC₅₀ value of 4.46 µg/mL (C.L.?=?2.002–9.947). Furthermore, Brine shrimp (Artemia salina) cytotoxicity bioassay showed that the larvae viability was significantly affected at higher concentrations than those capable to induce significant antioxidant and anti-acetylcholinesterase effects (LD₅₀ 25 µg/mL). The results suggest that polyphenols and terpenoids can contribute significantly to antioxidant and anti-acetylcholinesterase activities of E. dendroides latex.     

Dissection of the oligogenic resistance to Cucumber mosaic virus in the melon accession PI 161375

Resistance to Cucumber mosaic virus (CMV) in the exotic melon accession PI 161375, cultivar "Sonwang Charmi" (SC) had previously been described as oligogenic, recessive and quantitative, with a major QTL residing in linkage group XII (LGXII). We have used a collection of near isogenic lines (NILs) with introgressions of SC into the genome of the susceptible accession Piel de Sapo (PS) to further characterise this resistance. Infection of NILs carrying introgressions on LGXII showed that only NIL SC12-1 was resistant to CMV strains P9 and P104.82, but not to strains M6 and TL. Further mapping of this region showed that the resistance, named cmv1 maps in an area of 2.2 cM, between markers CMN61_44 and CMN21_55. Moreover, cmv1 confers total resistance to strains P9 and P104.82, indicating that in these cases it is not quantitative and that cmv1 is sufficient to confer full resistance to these CMV strains. Candidate gene mapping of ten translation initiation factors in the melon genome failed to find any of them in the interval between markers CMN61_44 and CMN21_55. All these results suggest that the resistance to CMV present in SC is oligogenic, where different loci confer resistance to different CMV strains, but not necessarily quantitative, since at least one of these genes (cmv1) confers total resistance, similar to that of the parental SC, and does not need the contribution of other loci.     

Antimycobacterial in vitro activity of cobalt(II) isonicotinoylhydrazone complexes. Part 10

Octahedral cobalt(II) complexes of isonicotinoylhydrazones, which were obtained from the primary antituberculous agent isoniazid, have been synthesised and characterised. Their antimycobacterial in vitro activity has been evaluated against Mycobacterium tuberculosis H37Rv: they exhibit MIC values ranging from < 0.1 to 0.39 microg/mL, showing them to be generally more active than previously reported analogous Cu(II) and Ni(II) complexes.     

Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones

Several (Z)-5-arylidene-2,4-thiazolidinediones were synthesized and tested as aldose reductase inhibitors (ARIs). The most active of the N-unsubstituted derivatives (2) exerted the same inhibitory activity of Sorbinil. The introduction of an acetic side chain on N-3 of the thiazolidinedione moiety led to a marked increase in lending inhibitory activity, conducting to the discovery of a very potent ARI (4c), whose activity level (IC50=0.13 microM) was in the same range of Tolrestat. Moreover, the corresponding methyl esters (3), devoid of any acidic functionality, showed appreciable inhibitory activity similar to that of the N-unsubstituted compounds. It was also found that the substitution pattern on the 5-benzylidene moiety markedly influenced the activity of N-unsubstituted 2,4-thiazolidinediones 2, compounds with substituents at the meta position being generally more effective than the para-substituted ones; however, this SAR was not evidenced in acetates 3 and acids 4.