Galectin-9 plasma levels reflect adverse hematological and immunological features in acute dengue virus infection

Background: Dengue virus (DENV) infection remains a major public health burden worldwide. Soluble mediators may play a critical role in the pathogenesis of acute DENV infection. Galectin-9 (Gal-9) is a soluble β-galactoside-binding lectin, with multiple immunoregulatory and inflammatory properties. Objective: To investigate plasma Gal-9 levels as a biomarker for DENV infection. Study design: We enrolled 65 DENV infected patients during the 2010 epidemic in the Philippines and measured their plasma Gal-9 and cytokine/chemokine levels, DENV genotypes, and copy number during the critical and recovery phases of illness. Results: During the critical phase, Gal-9 levels were significantly higher in DENV infected patients compared to healthy or those with non-dengue febrile illness. The highest Gal-9 levels were observed in dengue hemorrhagic fever (DHF) patients (DHF: 2464. pg/ml; dengue fever patients (DF): 1407. pg/ml; non-dengue febrile illness: 616. pg/ml; healthy: 196. pg/ml). In the recovery phase, Gal-9 levels significantly declined from peak levels in DF and DHF patients. Gal-9 levels tracked viral load, and were associated with multiple cytokines and chemokines (IL-1α, IL-8, IP-10, and VEGF), including monocyte frequencies and hematologic variables of coagulation. Further discriminant analyses showed that eotaxin, Gal-9, IFN-α2, and MCP-1 could detect 92% of DHF and 79.3% of DF, specifically (P < 0.01). Conclusion: Gal-9 appears to track DENV inflammatory responses, and therefore, it could serve as an important novel biomarker of acute DENV infection and disease severity

IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I kappa B-zeta in keratinocytes

In psoriasis lesions, a diverse mixture of cytokines is up-regulated that influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of IL-17A alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of six cytokines (IL-17A, TNF-alpha, IL-17C, IL-22, IL-36. and IFN-gamma) involved in psoriasis to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on the differences in the expression profiles of cells stimulated with six cytokines versus cells stimulated with only five cytokines lacking IL-17A. Furthermore, a specific IL-17A-induced gene, NFKBIZ, which encodes I kappa B-zeta, a transcriptional regulator for NF-kappa B, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis

Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons

Degradation of IFN receptor (IFNR) protein is one of the mechanisms to limit the extent of cellular responses to interferons. Tyrosine kinase 2 (TYK2), a JAK family kinase, has been reported to bind to and stabilize IFNR, indicating that TYK2 is a fundamental component of IFNR complex. Herein, we identified Jun activation domain-binding protein 1 (JAB1) as a new TYK2 binding partner and investigated its role in the regulation of IFN responses. siRNA knockdown of JAB1 resulted in suppression of IFN-induced phosphorylation of STAT proteins and their transcriptional activation. Importantly, JAB1 knockdown induced the activation of SCF ubiquitin ligase complex containing Cullin 1 (CUL1), as judged by the enhancement of covalent modification of CUL1 with the ubiquitin-like protein NEDD8, and markedly reduced the basal protein level of IFNR. In contrast, NEDD8 knockdown or inhibition of NEDD8 modification by NEDD8-activating enzyme inhibitor resulted in increased IFNR protein concomitantly with a reduction of NEDD8-modified CUL1. Furthermore, NEDD8-activating enzyme inhibitor treatment enhanced the susceptibility to IFN-alpha in HeLa cells. These data suggest that the NEDD8 modification pathway is involved in the proteolysis of IFNR and that JAB1 acts as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway

コナガの生物的防除に関する研究 : 4.卵寄生蜂2種の増殖能力に及ぼす温度の影響

The effect of temperature on the development of two egg parasitoids, Trichogramma chilonis and T. ostriniae, which attack the diamondback moth, were observed in the laboratory under the controlled conditions of constant temperatures (20℃, 24℃ and 28℃). The results are summarized as follows: 1. The longevity of the female adult of T. chilonis was significantly longer at 20℃ as compared with 24℃ and 28℃. 2. No significant difference in the female adult longevity of T. ostriniae was observed at 20℃, 24℃ and 28℃. 3. The fecundity of each parasitoid was significantly higher at 20℃ as compared with 24℃ and 28℃. 4. The two parasitoids were proved to be pro-ovigenic. 5. The percentage of offspring female production in the two egg parasitoids was highest from the eggs deposited on the first day of emergence and the trends were decreased thereafter towards the end of female's lifetime. 6. The values of capacity for increase (γ_c)risen as the temperature increased from 20℃ to 28℃. 7. The fecundity of each parasitoid was highest at the first day of emergence and then the trend was decreased toward the end of female lifetime.T.chilonisとT.ostriniaeの増殖能力に及ぼす温度の影響を調査した.その結果を要約すると以下の通りである.1.T.chilonisの成虫の寿命は,20℃では24℃と28℃区に比べて有意に長かった.2.T.ostriniaeの成虫の寿命は,どの温度区の間にも有意な差が認められなかった.3.両寄生蜂の産卵数は,20℃区では24℃と28℃区に比べて有意に多かった.4.両寄生蜂の卵巣発育様式はpro-ovigenic型である.5.両寄生蜂の羽化雌率は,親雌蜂の羽化直後に産下した卵で高く,日が経つにつれ低下していった.6.両寄生蜂の内的自然増加率は20℃から28℃へ温度が上がると高くなった.7.両寄生蜂の平均総産卵数は,寄主を与え始めた時の親雌蜂の日齢が若いほど多かった

Studies on the Biological Control of the Diamondback Moth, Plutella xylostella (Linnaeus) : 4. Effect of Temperature on the Development of the Egg-Parasitoids, Trichogramma chilonis and Trichogramma ostriniae

The effect of temperature on the development of two egg parasitoids, Trichogramma chilonis and T. ostriniae, which attack the diamondback moth, were observed in the laboratory under the controlled conditions of constant temperatures (20℃, 24℃ and 28℃). The results are summarized as follows: 1. The longevity of the female adult of T. chilonis was significantly longer at 20℃ as compared with 24℃ and 28℃. 2. No significant difference in the female adult longevity of T. ostriniae was observed at 20℃, 24℃ and 28℃. 3. The fecundity of each parasitoid was significantly higher at 20℃ as compared with 24℃ and 28℃. 4. The two parasitoids were proved to be pro-ovigenic. 5. The percentage of offspring female production in the two egg parasitoids was highest from the eggs deposited on the first day of emergence and the trends were decreased thereafter towards the end of female\u27s lifetime. 6. The values of capacity for increase (γ_c)risen as the temperature increased from 20℃ to 28℃. 7. The fecundity of each parasitoid was highest at the first day of emergence and then the trend was decreased toward the end of female lifetime.T.chilonisとT.ostriniaeの増殖能力に及ぼす温度の影響を調査した.その結果を要約すると以下の通りである.1.T.chilonisの成虫の寿命は,20℃では24℃と28℃区に比べて有意に長かった.2.T.ostriniaeの成虫の寿命は,どの温度区の間にも有意な差が認められなかった.3.両寄生蜂の産卵数は,20℃区では24℃と28℃区に比べて有意に多かった.4.両寄生蜂の卵巣発育様式はpro-ovigenic型である.5.両寄生蜂の羽化雌率は,親雌蜂の羽化直後に産下した卵で高く,日が経つにつれ低下していった.6.両寄生蜂の内的自然増加率は20℃から28℃へ温度が上がると高くなった.7.両寄生蜂の平均総産卵数は,寄主を与え始めた時の親雌蜂の日齢が若いほど多かった