Kyung-Won Kang

Immunomodulatory Potential of Weissella cibaria in Aged C57BL/6J Mice

Aging is associated with distinct changes in immune cells and a decline in immune function, leading to increased susceptibility to infection and reduced responses to vaccination. Certain strains of lactic acid bacteria exert beneficial effects on the immune system. Previously, we reported that Weissella cibaria JW15 isolated from kimchi possesses immune stimulatory activity in vitro. In the present study, we further investigated whether oral administration of JW15 improves immune function in aged mice. Eighteen-month-old female mice were administered JW15 daily at low (JW15-L; 1 × 10⁸ CFU/mouse) or high dosage (JW15-H; 1 × 10⁹ CFU/mouse), or with Lactobacillus rhamnosus GG (LGG) using oral gavage. Twomonth- old female mice were included as healthy young mice. After 4 weeks, the mice were euthanized and immune profiles were analyzed using whole blood and spleen. In complete blood count analysis, the numbers of white and red blood cells were significantly increased in the JW15-L group compared with those in the old mouse (OM) control group. In addition, administration of either JW15 of LGG resulted in higher numbers of splenocytes in comparison with the OM group. Furthermore, proliferative potentials were higher in all probiotic groups than OM. Cytokines such as IFN-γ and IL-6 were secreted at higher levels in splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA expression of various cytokines was altered in the JW15 groups. Collectively, these results suggest that JW15 supplementation induces immunomodulatory effects in aged mice and indicate JW15 as a potential probiotic strain to improve immune function in aged animals.

IK acts as an immunoregulator of inflammatory arthritis by suppressing T H 17 cell differentiation and macrophage activation

Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.

Effect of apoptosis-associated speck-like protein containing a caspase recruitment domain on vaccine efficacy: Overcoming the effects of its deficiency with aluminum hydroxide adjuvant: Role of ASC in vaccine efficacy

Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine‐induced humoral and cell‐mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC) is one of the main components of inflammasomes, but it is not clear whether ASC affects the vaccine‐induced immune response. Herein, we used two types of vaccines: inactivated influenza vaccine not formulated with alum, and HPV vaccine formulated with alum. We gave the vaccines to ASC knockout (ASC−/−) mice to investigate the role of ASC in vaccine efficacy. Influenza vaccine‐immunized ASC−/− mice did not show antibody titers in week 2 after the first vaccination. After boosting, the antibody titer in ASC−/− mice was about half that in wild type (WT) mice. Furthermore, a cytotoxic T‐lymphocyte response against influenza vaccine was not induced in ASC−/− mice. Therefore, vaccinated ASC−/− mice did not show effective protection against viral challenge. ASC−/− mice immunized with alum‐formulated HPV vaccine showed similar antibody titers and T‐cell proliferation compared with immunized WT mice. However, the HPV vaccine without alum induced up to threefold lower titers of HPV‐specific antibody titers in ASC−/− mice compared with those in WT mice. These findings suggest that alum in vaccine can overcome the ASC‐deficient condition.

Huge Abdominal Cyst Occurred After Kidney Transplantation

This case demonstrates continuous ambulatory peritoneal dialysis-related endometrial tissue migration and occurrence of huge cystic endometriosis by the recovery of menstrual period after kidney transplantation.

SPA0355 suppresses T-cell responses and reduces airway inflammation in mice.

In recent studies, SPA0355, a thiourea analog, has been demonstrated to possess strong anti-inflammatory activity. However, the mechanisms underlying the effects of SPA0355 on immune-mediated diseases have not been fully defined. The present study was designed to investigate the immunological and molecular mechanisms by which SPA0355 modulates cluster of differentiation of (CD4)(+) T-cell-mediated immune responses in allergic airway inflammation. In vitro studies have shown that SPA0355 suppresses CD4(+) T-cell activation, proliferation, and differentiation via modulation of T-cell receptor (TCR) signal transduction and cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Next, we investigated the efficacy of SPA0355 in ovalbumin (OVA)-induced allergic airway inflammation. Intraperitoneal administration of SPA0355 inhibited inflammatory cell recruitment into the airways as well as the production of Th2 cytokines in bronchoalveolar fluid and suppressed OVA-induced IgE production in serum. Additionally, SPA0355 suppressed mucin production and smooth muscle hypertrophy and prevented the development of airway hyperresponsiveness. Given that allergic airway inflammation is mainly driven by Th2 cell responses, it is highly possible that the defects in CD4(+) T-cell activation and Th2 cell differentiation in the draining lymph nodes and suppressed NF-κB activation in the lungs of SPA0355-treated mice illustrate an immunological mechanism of the preventive effect of SPA0355 on the aforementioned asthmatic characteristics. Collectively, our results suggest that SPA0355 directly modulates Th1 and Th2 responses through the suppression of multiple signaling pathways triggered by TCR or cytokine receptor stimulation, and that SPA0355 has protective effects in a murine model of allergic airway inflammation.

The Case | Acute renal failure after laparoscopic nephrectomy

W Kim, KP Kang, SM Kang, S Lee, DH Kim, SY Lee, YB Jeong, HJ Kim, MH Sohn and SK Park Renal Regeneration Laboratory and Department of Internal Medicine, Jeonju, Republic of Korea; Department of Radiology, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; Department of Urology, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea and Department of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea