Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling

Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subsequently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)-1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF-1α regulates sphingosine 1-phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF-1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF-1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of monocytes/macrophages in response to circulating HIF-1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing

Macrophage Motility in Wound Healing Is Regulated by HIF-1 alpha via S1P Signaling

Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subsequently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)-1 alpha is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF-1 alpha regulates sphingosine 1-phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF-1 alpha have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF-1 alpha/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of monocytes/macrophages in response to circulating HIF-1 alpha is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing

Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling

Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subsequently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)-1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF-1α regulates sphingosine 1-phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF-1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF-1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of monocytes/macrophages in response to circulating HIF-1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing

Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling

Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subsequently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)-1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF-1α regulates sphingosine 1-phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF-1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF-1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of monocytes/macrophages in response to circulating HIF-1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing

HIF-1 alpha controls palatal wound healing by regulating macrophage motility via S1P/S1P(1) signaling axis

Objectives To investigate the role of hypoxia-inducible factor 1 alpha (HIF-1 alpha) signaling, the expression profile of M1 and M2 macrophages, and the role of the sphingosine 1-phosphate (S1P)/S1P receptor system in palatal wound healing of heterozygous HIF-1 alpha-deficient (HIF-1 alpha HET) mice. Materials and methods HIF-1 alpha HET and wild-type (WT) littermates underwent palatal tissue excision at the mid-hard palate. Histological analysis, immunostaining, real-time PCR, Western blotting (WB), and cellular migration assays were performed to analyze wound closure and macrophage infiltration. Results DMOG pretreatment showed an acceleration of palatal wound closure in WT mice. In contrast, the delayed palatal wound closure was observed in HIF-1 alpha HET mice with diminished production of Col1a1, MCP-1, and MIP-1 alpha, compared with WT mice. Decreased infiltration of M1 macrophage (F4/80(+)TNF-alpha(+), F4/80(+)iNOS(+)) and M2 macrophage (F4/80(+)Arginase-1(+), F4/80(+)CD163(+)) was observed. The numbers of F4/80(+)S1P(1)(+) macrophages of HIF-1 alpha HET wounded tissues were significantly lower compared with WT tissues. S1P treatment of bone marrow macrophages (BMMs) significantly upregulated expression of S1P(1) in WT mice compared with HIF-1 alpha HET. Phosphorylation of MAPK rapidly decreased in BMMs of HIF-1 alpha HET mice than in BMMs of WT mice by S1P stimulation. Moreover, S1P enhanced HIF-1 alpha expression via S1P(1) receptors to affect macrophage migration. Conclusions HIF-1 alpha deficiency aggravates M1 and M2 macrophage infiltration and controls macrophage motility via S1P/S1P(1) signaling. These results suggest that HIF-1 alpha signaling may contribute to the regulation of palatal wound healing

Are forested buffers an effective conservation strategy for riparian fauna? An assessment using meta-analysis

Historically, forested riparian buffers have been created to provide protection for aquatic organisms and aquatic ecosystem functions. Increasingly, new and existing riparian buffers are being used also to meet terrestrial conservation requirements. To test the effectiveness of riparian buffers for conserving terrestrial fauna, we conducted a meta-analysis using published data from 397 comparisons of species abundance in riparian buffers and unharvested (reference) riparian sites. The response of terrestrial species to riparian buffers was not consistent between taxonomic groups; bird and arthropod abundances were significantly greater in buffers relative to unharvested areas, whereas amphibian abundance decreased. Edge-preferring species were more abundant in buffer sites than reference sites, whereas species associated with interior habitat were not significantly different in abundance. The degree of buffer effect on animal abundance was unrelated to buffer width; wider buffers did not result in greater similarity between reference and buffer sites. However, responses to buffer treatment were more variable in buffers ,50 m wide, a commonly prescribed width in many management plans. Our results indicate that current buffer prescriptions do not maintain most terrestrial organisms in buffer strips at levels comparable to undisturbed sites

Origin of carbon and essential fatty acids in higher trophic level fish in headwater stream food webs

Dietary carbon sources in headwater stream food webs are divided into allochthonous and autochthonous organic matters. We hypothesized that: 1) the dietary allochthonous contribution for fish in headwater stream food webs positively relate with canopy cover; and 2) essential fatty acids originate from autochthonous organic matter regardless of canopy covers, because essential fatty acids, such as 20:5ω3 and 22:6ω3, are normally absent in allochthonous organic matters. We investigated predatory fish Salvelinus leucomaenis stomach contents in four headwater stream systems, which are located in subarctic region in northern Japan. In addition, stable carbon and nitrogen isotope ratios, fatty acid profile, and stable carbon isotope ratios of essential fatty acids were analyzed. Bulk stable carbon analysis showed the major contribution of autochthonous sources to assimilated carbon in S. leucomaenis. Surface baits in the stomach had intermediate stable carbon isotope ratios between autochthonous and allochthonous organic matter, indicating aquatic carbon was partly assimilated by surface baits. Stable carbon isotope ratios of essential fatty acids showed a positive relationship between autochthonous sources and S. leucomaenis across four study sites. This study demonstrated that the main supplier of dietary carbon and essential fatty acids was autochthonous organic matter even in headwater stream ecosystems under high canopy cover

Hormonal Therapy Resistant Estrogen-receptor Positive Metastatic Breast Cancer Cohort (HORSE-BC) Study : Current Status of Treatment Selection in Japan

The Hormonal therapy resistant estrogen-receptor positive metastatic breast cancer cohort (HORSE-BC) study is a multicenter observational study evaluating the efficacy and safety of secondary endocrine therapy (ET) for postmenopausal cases of metastatic breast cancer (MBC) with poor response to primary ET. In this initial report we analyze the HORSE-BC baseline data to clarify the current status of treatment selection for MBC in Japan. Baseline data for the 50 patients enrolled in HORSE-BC were analyzed, including patient characteristics, types of secondary ET, and reasons for selecting secondary ET. Postoperative recurrence was detected in 84% of patients (42/50) and de novo stage IV breast cancer in 16% (8/50). Forty-one patients (41/50; 82%) received fulvestrant, 5 patients (10%) received selective estrogen receptor modulators (SERMs), 3 patients (6%) received ET plus a mammalian target of rapamycin (mTOR) inhibitor, and 1 patient received an aromatase inhibitor (AI) as the secondary ET. Forty-five patients selected their secondary ET based on its therapeutic effect, while 14 patients selected it based on side effects. Most patients with progression after primary ET selected fulvestrant as the secondary ET based on its therapeutic and side effects. We await the final results from the HORSE-BC study

Prospective cohort study of febrile neutropenia in breast cancer patients administered with neoadjuvant and adjuvant chemotherapies: CSPOR-BC FN study

Background As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). Patients and methods Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians’ discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. Results Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. Conclusions FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC

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特集1 海中工学研究センタ