Lamina propria macrophages (LPMϕs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation of immune responses against commensal bacteria. MCP-1 is a chemokine that plays an important role in recruitment of monocytes and macrophages to inflamed tissues. We demonstrated that, in addition to IL-10, LPMϕs produced large amounts of MCP-1, even in a steady state. MCP-1 deficiency caused impaired IL-10 production by LPMϕs and led to exacerbation of dextran sulfate sodium-induced acute colitis. As an explanation of this impaired IL-10 production by LPMϕs, we found that LPMϕs could be separated into two subsets with distinct side-scattered properties, namely LPMϕ1 (CD11b+F4/80+CD11c–SSChi) and LPMϕ2 (CD11b+F4/80+CD11c–SSClo). Unlike LPMϕ1, the LPMϕ2 subset migrated in response to MCP-1 and produced a larger amount of IL-10 in response to commensal bacteria. LPMϕs isolated from MCP-1–deficient mice produced less IL-10 as a consequence of the lack of the MCP-1–dependent LPMϕ2 population. This imbalanced composition in LPMϕ population may be involved in the susceptibility to DSS-induced colitis in MCP-1–deficient mice. Our results suggest that endogenous MCP-1 contributes to the composition of resident LPMϕ subsets in the intestine. Moreover, MCP-1–dependent LPMϕ2 subset may play an important role in maintenance of gut homeostasis in the steady state, and in the termination of excess inflammatory responses in the intestine, by producing IL-10.
The genes coding for two structurally different isocitrate dehydrogenase isozymes (IDH-I and IDH-II) of a psychrophilic bacterium, Vibrio sp. strain ABE-1, were cloned and sequenced. Open reading frames of the genes (iedI and iedII) are 1,248 and 2,229 bp in length, respectively. The amino acid sequences predicted from the open reading frames of iedI and icdII corresponded to the N-terminal amino acid sequences of the purified IDH-I and IDH-II, respectively. No homology was found between the deduced amino acid sequences of the isozymes; however, the IDH-I, a dimeric enzyme, had a high amino acid sequence identity (74.3%) (18,25). One, IDH-I, is a homodimer of thermostability comparable to that of the enzymes from mesophiles, and the other, IDH-II, is a monomer with extreme lability above 20°C. In addition, immunochemical properties and N-terminal amino acid sequences of the isozymes have been shown to be different from each other (18) but showed similarities to those of the respective types of other bacterial IDHs (12).The genes encoding dimeric IDHs of E. coli (35) and T thermophilus (21) have been cloned and sequenced, respectively. There is significant homology between these predicted amino acid sequences, and the amino acid residues which are suggested to interact with isocitrate (17) are also conserved in the two enzymes. Recently, homology between the deduced amino acid sequences of Saccharomyces cerevisiae (9) heart (32) mitochondrial IDHs were reported to be very high, but the eucaryotic enzymes exhibit low amino acid sequence similarity to the E. coli IDH. However, Soundar and Colman (32) reported that the amino acid residues which are implicated in metal-isocitrate binding in the E. coli enzyme (17) are located in the same general region of the eucaryotic enzymes. These findings have implications for the molecular evolution of IDH. But the relation between dimeric and monomeric IDHs is still unclear, since no sequence of a monomeric IDH has been determined.Since Vibrio sp. strain ABE-1 possesses structurally different IDH isozymes (18,25), investigation of the genes encoding the isozymes is necessary to elucidate the physiological and evolutionary basis of the coexistence of the isozymes at the molecular level. In this paper, we report the cloning and sequencing of the genes coding for the IDH isozymes. It was found that the two genes are closely adjacent, and the predicted amino acid sequence of the IDH-I is very similar to that of the E. coli enzyme but quite different from that of IDH-II. Some regulatory aspects of the expression of the cloned genes are also presented. MATERIALS AND METHODS Materials
The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers.
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