Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.Following the well-known epidemiological study conducted in Northwest Greenland in the 1970s (Dyerberg et al., 1978), several clinical assessments have indicated that a diet rich in ω3 polyunsaturated fatty acids (PUFAs) has beneficial effects in various inflammatory diseases, including asthma, psoriasis, inflammatory bowel diseases, and rheumatoid arthritis (Horrobin, 1987). Although it remains unclear how ω3 PUFAs exert such antiinflammatory effects, recent studies have identified several derivatives of ω3 PUFAs that possess strong antiinflammatory effects (Serhan et al., 2008; Tull et al., 2009). Resolvin E1 (RvE1) is one such antiinflammatory lipid mediator.RvE1 is known to exert its actions through two receptors, BLT1 and ChemR23 (Arita et al., 2007). RvE1 binds to BLT1, a G protein–coupled receptor for leukotriene B4 (LTB4), and inhibits BLT1 signals (Arita et al., 2007). In addition, RvE1 exhibits an agonistic activity toward ChemR23 (Arita et al., 2007), a G protein–coupled receptor for chemerin. The antiinflammatory effects of RvE1 have been demonstrated in acute innate immune inflammation, such as peritonitis (Arita et al., 2007) and colitis (Arita et al., 2005b). In these models, RvE1 exerted its antiinflammatory effects by inhibiting neutrophil infiltration into the inflammatory foci through a blockade of LTB4-BLT1 signaling in neutrophils (Haas-Stapleton et al., 2007). In contrast, few studies have been conducted on the effect of RvE1 on acquired immune responses, in which DCs and T cells play major roles in the development. In these studies, the attenuated cytokine production, such as IL-12 and IL-23, from DCs is considered as the major mechanism by which RvE1 exerts the antiinflammatory effects (Arita et al., 2005a; Haworth et al., 2008). However, the effect of RvE1 on DC motility has not been investigated in the context of acquired immunity.In the peripheral tissues such as the skin, DCs migrate in an amoeboid movement that requires actin polymerization via activation of the Rho family of small GTPases, such as Cdc42, Rac, and Rho A (Lämmermann and Germain, 2014). In acquired immunity such as contact hypersensitivity (CHS), upon uptake of foreign antigens, DCs migrate to the draining LNs (dLNs) via lymphatic vessels to establish sensitization by inducing the antigen-specific T cell differentiation (Honda et al., 2013). In elicitation, DC migration to form DC–T cell clustering is required for efficient antigen presentation in situ (Natsuaki et al., 2014). Thus, active DC motility is an essential factor for acquired immunity.In this study, we investigated the effects and underlying mechanisms of RvE1 on DC motility using a CHS model, which is a prototype of delayed-type hypersensitivity in the skin mediated by IFN-γ (Mori et al., 2008; Honda et al., 2013). RvE1 inhibited cutaneous DC migration into the dLNs and suppressed antigen-specific T cell induction in the sensitization phase. In addition, live imaging analysis revealed that RvE1 inhibited cutaneous DC motility and cluster formation in the skin, which subsequently attenuated activation of effector T cells in the skin in the elicitation phase of CHS. Intriguingly, LTB4 induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. These results suggest that RvE1 exerts its antiinflammatory effects in cutaneous acquired immunity by inhibiting DC motility, possibly through an LTB4-BLT1 signaling blockade.     

Recurrent hepatocellular carcinoma with tumor thrombus in right atrium - report of a successful liver resection with tumor thrombectomy using total hepatic vascular exclusion without concomitant cardiopulmonary bypass

For resection of advanced hepatocellular carcinoma (HCC) in which tumor thrombus (TT) extends into inferior vena cava (IVC) or right atrium (RA) surgery is challenging and requires skillful techniques. Here, we report a case of recurrent HCC with TT extending to the RA, who underwent successful resection with tumor thrombectomy without concomitant cardiopulmonary bypass. A 71-year-old man, who had been followed- up for hepatitis C by a local hospital, was diagnosed as having HCC in segment 6 for which he had undergone segmentectomy of segment 6 in May 2009. During follow-up, he developed severe leg edema and ascites with investigations revealing recurrent HCC in segment 7 with TT extending to the right atrium via IVC. After transarterial embolization the patient underwent extended resection of the segment 7 with tumor thrombectomy of the IVC and the right atrium and partial resection of the IVC wall using total hepatic vascular exclusion, without concomitant cardiopulmonary bypass. Total ischemic time was 23 minutes, operation time was 6 hours and blood loss was 2,474mL. The postoperative course was uneventful. Histopathology was recurrent hepatocellular carcinoma with hepatic venous invasion. We report the case of resected recurrent HCC with TT extending to right atrium without concomitant cardiopulmonary bypass.     

Cone-beam computed tomography for the diagnosis of mandibular condylar fractures: 11 case reports

The temporomandibular joint has many complex anatomical and functional features compared with other joints. Therefore, caution should be exercised in the diagnosis of temporomandibular joint fractures. Although panoramic tomography is widely used for the screening of orofacial trauma as well as other diseases, this modality often overlooks evidence of a condylar fracture. Cone-beam computed tomography is also used for diagnosing orofacial diseases. The purposes of this report are to show the usefulness of cone-beam computed tomography in diagnosing condylar fractures and to describe the imaging features of condylar fractures.     

Expression of GLUT-1 and GLUT-3 in Xanthogranulomatous Cholecystitis Induced a Positive Result on 18F-FDG PET: Report of a Case

Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of ¹⁸F-FDG PET are not specific for malignancy because ¹⁸F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for ¹⁸F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on ¹⁸F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on ¹⁸F-FDG PET.