Cytokine cross-talk between phagocytic cells and lymphocytes: Relevance for differentiation/activation of phagocytic cells and regulation of adaptive immunity

Cytokines represent one of the most important elements in the communication among different cell types. They play an increasingly better understood role in the communication among hematopoietic cells and in particular in the reciprocal regulation of effector cell types of innate or natural resistance (phagocytic cells and Natural Killer (NK) cells) and those of adaptive immunity (T and B lymphocytes). Lymphocytes produce several cytokines with either stimulatory (e.g., colony stimulatory factor) or suppressive (e.g., tumor necrosis factors and interferons) effects on proliferation of early hematopoietic cells. Many of these cytokines, alone or acting in synergistic combinations, also have a differentiation-inducing ability on immature myeloid cells and act as powerful potentiators of the cellular functions of terminally differentiated phagocytic cells. The communication between lymphocytes and phagocytic cells is not unidirectional, as phagocytic cells produce factors that regulate lymphocyte activation. In addition to their role as antigen presenting cells expressing costimulatory accessory molecules and secreting cytokines (e.g., IL-1, IL-6, TNF), phagocytic cells have been recently shown to produce Natural Killer cell Stimulatory Factor (NKSF/IL-12). IL-12 is a heterodimeric cytokine with important modulatory functions on cytotoxicity of NK and T cells, lymphocyte proliferation, lymphokine production, and development of T helper cell subsets. These communications between phagocytic cells and lymphocytes are further regulated by negative and positive feedback mechanisms that contribute to maintain the homeostasis of the system in physiologic conditions and to govern the changes in this equilibrium needed for the response to infectious or other foreign agents.     

Hastifolins A–G,antifeedant neo-clerodane diterpenoids from Scutellaria hastifolia

From the aerial parts of Scutellaria hastifolia, family Lamiaceae (Labiatae), seven neo-clerodane diterpenoids (hastifolins A–G) were isolated. The products are similar to the known scuteparvin and are characterized by being trans-cinnamoyl derivatives. Structures and stereochemistry were determined by intensive NMR investigation. Six of the products form three pairs of epimers at C-13. Hastifolins A–C showed significant antifeedant activity.     

TNFA Haplotype Genetic Testing Improves HLA in Estimating the Risk of Celiac Disease in Children

Background

TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner.

Methods

511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence).

Results

Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations.

Conclusion

TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk.     

Dietary Total Antioxidant Capacity and Colorectal Cancer in the Italian EPIC Cohort

Background

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.

Methods

We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.

Results

Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44–0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19–3.66; 3rd tertile 2.48 95%CI: 1.32–4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.

Conclusions

Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.     

A volatile Pb(II) β-Diketonate diglyme complex as a promising precursor for MOCVD of lead oxide films

A polyether adduct of the lead(II) hexafluoroacetylacetonate has been synthesized and characterized by elemental analysis, NMR spectroscopy, mass spectrometry and infrared spectroscopy. The single crystal X-ray diffraction study provides evidence of a dimeric structure of the type [Pb(hfa)₂ · diglyme]₂ (Hhfa=1,1,1,5,5,5-hexafluoro-2,4-pentanedione, diglyme=CH₃O(CH₂CH₂O)₂CH₃). The thermal analyses have revealed high volatility and good thermal stability with a low residue despite the dimeric nature of the adduct. This novel compound has been successfully applied as a precursor for the depositions of PbO films. It represents the first example of lead precursors that can be used in the liquid phase without decomposition, thus providing constant evaporation rates even for very long deposition times.