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After birth, the development of secondary lymphoid tissues (SLTs) in the colon is dependent on the expression of the aryl hydrocarbon receptor (AhR) in immune cells as a response to the availability of AhR ligands. However, little is known about how AhR activity from intestinal epithelial cells (IECs) may influence the development of tertiary lymphoid tissues (TLTs). As organized structures that develop at sites of inflammation or infection during adulthood, TLTs serve as localized centers of adaptive immune responses, and their presence has been associated with the resolution of inflammation and tumorigenesis in the colon. Here, we investigated the effect of the conditional loss of AhR activity in IECs in the formation and immune cell composition of TLTs in a model of acute inflammation. In females, loss of AhR activity in IECs reduced the formation of TLTs without significantly changing disease outcomes or immune cell composition within TLTs. In males lacking AhR expression in IECs, increased disease activity index, lower expression of functional-IEC genes, increased number of TLTs, increased T-cell density, and lower B- to Tcell ratio were observed. These findings may represent an unfavorable prognosis when exposed to dextran sodium sulfate (DSS)-induced epithelial damage compared with females. Sex and loss of IEC AhR also resulted in changes in microbial populations in the gut. Collectively, these data suggest that the formation of TLTs in the colon is influenced by sex and AhR expression in IECs. NEW & NOTEWORTHY This is the first research of its kind to demonstrate a clear connection between biological sex and the development of tertiary lymphoid tissues (TLT) in the colon. In addition, the research finds that in a preclinical model of inflammatory bowel disease, the expression of the aryl hydrocarbon receptor (AhR) influences the development of these structures in a sex-specific manner [ABSTRACT FROM AUTHOR]

Background Tolfenamic acid ( TA) is an NSAID currently under investigation as an anticancer agent in humans. TA induces proteosome-dependent degradation of transcription factors Sp 1, 3, and 4. These proteins are known to be overexpressed in many human cancers. Hypothesis To evaluate the protein expression of Sps in canine tissue, and efficacy of TA against several canine tumor cell lines. Methods Six canine cell lines (2 osteosarcoma, 2 mammary carcinoma, 2 melanoma) were evaluated. Protein levels of Sp 1-4 and their downstream targets were evaluated using Western Blots. Cell survival and TUNEL assays were performed on cell lines, and Sp1 expression was evaluated on histologic samples from archived canine cases. Animals Six immortalized canine cancer cell lines derived from dogs were used. Archived tissue samples were also used. Results Sps were highly expressed in all 6 cell lines and variably expressed in histologic tissues. TA decreased expression of Sps 1-4 in all cell lines. All of the downstream targets of Sps were inhibited in the cell lines. Variable Sp1 expression was identified in all histologic samples examined. TA significantly inhibited cell survival in all cell lines in a dose dependant fashion. The number of cells undergoing apoptosis was significantly increased ( P < .05) in all cell lines after exposure to TA in a dose-dependent fashion. Conclusions, and Clinical Importance Tolfenamic acid is a potential anticancer NSAID and further investigation is needed to determine its usefulness in a clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: 1,1-Bis(3-indolyl)-1-(p-substituted phenyl)methanes (C-DIMs) substituted in the phenyl ring with a para-, t-butyl, trifluoromethyl (DIM-C-pPhCF(3)) or phenyl (DIM-C-pPhC(6)H(5)) group activate peroxisome proliferator-activated receptor gamma (PPARgamma) in several cancer cell lines, and DIM-C-pPhCF(3) also activates the orphan receptor Nur77. In this study, we have examined the effects of 5,5'-dihydroxy, 5,5'-dimethyl, 5,5'-dibromo, 5,5'-dinitro and 5,5'-dimethoxyindole ring-substituted analogs of DIM-C-pPhC(6)H(5) on their activity as PPARgamma agonists.Methods: Various substituted C-DIM analogs were used to investigate their growth-inhibitory activities and activation of PPARgamma-mediated transactivation in colon and pancreatic cancer cells. Their structure-dependent induction of putative PPARgamma-responsive genes/proteins including p21, KLF-4 and caveolin1 were also determined by Western and Northern blot analysis.Results: Introduction of the 5,5'-dihydroxy and 5,5'-dimethyl substituents enhanced activation of PPARgamma in colon and pancreatic cancer cells. However, activation of p21 in Panc28 pancreatic cancer cells and induction of caveolin-1 and KLF4 in colon cancer cells by the C-DIM compounds were structure- and cell context-dependent.Conclusions: The results demonstrate that DIM-C-pPhC(6)H(5) and indole ring-substituted analogs are selective PPARgamma modulators. [ABSTRACT FROM AUTHOR]

The lipid levels of the fungus Mucor rouxii are affected markedly by both the growth temperature and the age of the cells. Both chloroform-methanol extractable (fraction I) and alkali extractable (fraction II) fatty acids are present in these cells, and the fraction II/fraction I ratio increased significantly with decreasing growth temperature. This ratio was, however, reasonably constant during the entire growth period at each specific growth temperature. In all cases, the unsaturation index of the fraction II fatty acids was significantly lower than the corresponding value for the fraction I fatty acids. Examination of the unsaturation indeces of the two fractions during the early log-phase growth period (48 hrs) indicated that the indeces decreased with increasing growth temperature; however, as the age of the cells increased, this relationship changed dramatically. At the end of 144 hrs growth, the unsaturation index for fraction II has reversed its temperature dependance completely, since the index is a maximum at the higher growth temperature. The degree of unsaturation for fraction I is a maximum at 25 C and is lower for cells grown at 15 and 35 C; this relationship is true between 96-144 hr after inoculation. [ABSTRACT FROM AUTHOR]

The effect of aerobic and oxygen limiting (anaerobic) growth conditions upon the fatty acid and lipid composition of Mucor rouxii has been examined. The aerobic cells contained a range of fatty acids typical of phycomycetes, i.e. γ-linolenic acid, with an unsaturation index of 1.20, whereas the anerobic cells contained relatively high levels of shorter chained fatty acids and very low concentrations of unsaturated acids (unsaturation index=0.025). The unsaturated compounds were monoolefinic tetra-, hexa-, and octadecenoic acids; and closer examination of their di-trimethylsilyl derivatives by gas chromatography and mass spectrometry showed that all three acids contained the double bond in the Δ position. These results were consistent with a microaerobic biosynthetic pathway. In addition, there were major quantitative differences in the lipid composition of the two types of cells; and it was evident that the differences in growth environment markedly affected the cellular lipid and fatty acid compositions. [ABSTRACT FROM AUTHOR]