Review
Multidisciplinary Sciences
Samuel Weeks, Rebecca Harris, Mobin Karimi
Summary: This review explores the role of ITK signaling in multiple diseases, including T cell-derived malignancies, allergic diseases, infectious diseases, autoimmune disorders, and the potential use of ITK inhibition in transplantation recipients.
Article
Biochemistry & Molecular Biology
Zoltan Hajnady, Mate Nagy-Penzes, Mate A. Demeny, Katalin Kovacs, Tarek El-Hamoly, Jozsef Maleth, Peter Hegyi, Zsuzsanna Polgar, Csaba Hegedus, Laszlo Virag
Summary: In this study, we investigated the role of OGG1 in acute pancreatitis (AP). Our results showed that the OGG1 inhibitor TH5487 reduced edema formation, inflammatory cell migration, and necrosis in a mouse model of cerulein-induced AP. TH5487 also caused accumulation of 8-oxoG and reduced tissue poly(ADP-ribose) levels. Furthermore, TH5487 shifted cell death from necrosis to apoptosis in isolated pancreatic acinar cells. The treatment with TH5487 suppressed the expression of various cytokine and chemokine mRNAs in the AP model. Additionally, we found that the transcriptional inhibitory effect of the OGG1 inhibitor may be due to impaired target site occupancy of NF-kappa B. Overall, OGG1 inhibition provides protection against tissue injury in AP through interference with the PARP1 and NF-kappa B activation pathways.
Article
Multidisciplinary Sciences
Manzhi Zhao, Ling Li, Caoimhe H. Kiernan, Melisa D. Castro Eiro, Floris Dammeijer, Marjan van Meurs, Inge Brouwers-Haspels, Merel E. P. Wilmsen, Dwin G. B. Grashof, Harmen J. G. van de Werken, Rudi W. Hendriks, Joachim G. Aerts, Yvonne M. Mueller, Peter D. Katsikis
Summary: Modulating chronic antigen stimulation and T-cell receptor signaling with an ITK inhibitor can reverse ICB resistance in solid tumors and enhance the effectiveness of ICB therapy.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Vasiliki Economopoulos, Maria Pannell, Vanessa A. Johanssen, Helen Scott, Kleopatra E. Andreou, James R. Larkin, Nicola R. Sibson
Summary: Research on breast cancer brain metastasis has revealed the potential therapeutic strategy of switching blood-derived macrophages and microglia towards a more pro-inflammatory phenotype to reduce tumor burden in the brain. Studies have shown that inhibiting the anti-inflammatory phenotype of these immune cells can significantly impact tumor growth in both in vitro and in vivo models.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Liyan Bai, Hae Jin Kee, Sin Young Choi, Young Mi Seok, Gwi Ran Kim, Seung-Jung Kee, Hyun Kook, Myung Ho Jeong
Summary: The genetic deletion of HDAC5 and treatment with class IIa HDAC inhibitors can prevent increases in blood pressure and arterial wall thickness induced by Ang II. HDAC5 plays a role in vascular contraction and hypertrophy, and its inhibition may be a potential target for hypertension treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Anesthesiology
Sarah A. Najjar, Lindsay L. Ejoh, Emanuel Loeza-Alcocer, Brian S. Edwards, Kristen M. Smith-Edwards, Ariel Y. Epouhe, Michael S. Gold, Brian M. Davis, Kathryn M. Albers
Summary: Recent studies indicate that the colon epithelium plays a significant role in regulating pain and hypersensitivity, inhibition of the epithelium can alleviate visceral sensitivity and inflammatory bowel disease-induced hypersensitivity, highlighting the potential of targeting the colon epithelium for pain treatment.
Article
Biochemistry & Molecular Biology
Barbara Meier-Schiesser, Mark Mellett, Marigdalia K. Ramirez-Fort, Julia-Tatjana Maul, Annika Klug, Nicola Winkelbeiner, Gabriele Fenini, Peter Schafer, Emmanuel Contassot, Lars E. French
Summary: Apremilast demonstrated significant therapeutic effects in a psoriasis mouse model and human cells, showing remarkable improvements in reducing skin lesions and inhibiting inflammatory responses. While not directly affecting inflammasome activation, the indirect benefits of PDE4 inhibition were evident in reducing inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Xinyue Huang, Shuixia Tan, Yanxia Li, Shuangyi Cao, Xingyan Li, Heling Pan, Bing Shan, Lihui Qian, Junying Yuan
Summary: Our study reveals a biphasic model of the role of RIPK1 in mediating proinflammatory cytokine production, with distinct temporal roles when caspases are inhibited. Early phase production is NF-κB pathway-mediated and scaffold-dependent, while late phase involves the formation of a novel complex with key signaling mediators. RIPK1 kinase inhibitor Nec-1s can block late phase cytokine production, demonstrating a mechanism for the regulation of inflammatory signaling.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zhangfu Fang, Fang Yi, Yang Peng, Junfeng (Jim) Zhang, Liting Zhang, Zheng Deng, Fagui Chen, Chenhui Li, Yaowei He, Chuqin Huang, Qingling Zhang, Kefang Lai, Jiaxing Xie
Summary: The study demonstrated that the TRPA1 antagonist HC-030031 reduced airway inflammation and hyperresponsiveness in a murine allergic rhinitis model by targeting TRPA1, leading to decreased type-2 inflammation in nasal mucosa and improved nose-scratching events, as well as reduced leucocyte numbers and IL-8 levels in the BAL fluid.
Article
Biochemistry & Molecular Biology
David Schumacher, Adelina Curaj, Sakine Simsekyilmaz, Andreas Schober, Elisa A. Liehn, Sebastian F. Mause
Summary: The study found that genetic depletion of miR155 in a dyslipidemic mouse model of myocardial infarction does not reduce infarction size and consecutive heart failure, but it does decrease myofibroblast density in the post-ischemic scar.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Shunhui Wei, Bo Chen, See Wee Low, Charlene Priscilla Poore, Yahui Gao, Bernd Nilius, Ping Liao
Summary: Neuronal swelling is a pathological feature of stroke caused by aberrant accumulation of sodium and chloride ions inside neurons. SLC26A11 was identified as the major chloride entry pathway under hypoxia and blocking its activity could reduce chloride entry and attenuate hypoxia-induced neuronal swelling. Inhibition of SLC26A11 could be a novel therapeutic strategy for stroke.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Immunology
Ahmed Nadeem, Sheikh F. Ahmad, Naif O. Al-Harbi, Khalid E. Ibrahim, Wedad Sarawi, Sabry M. Attia, Abdullah F. Alasmari, Saleh A. Alqarni, Ali S. Alfradan, Saleh A. Bakheet, Mohammad M. Al-Harbi
Summary: Acute kidney injury (AKI) is a global health issue with increasing incidence, mainly due to renal tubular injury causing rapid deterioration of renal function. Immune system dysfunction induced by sepsis plays a key role in AKI, releasing pro-inflammatory cytokines and leading to renal inflammation. Inhibition of ITK signaling may be an effective strategy to prevent renal dysfunction associated with AKI.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Andreas Koller, Susanne Maria Brunner, Julia Preishuber-Pfluegl, Daniela Mayr, Anja-Maria Ladek, Christian Runge, Herbert Anton Reitsamer, Andrea Trost
Summary: The endosomal-lysosomal system (ELS), essential for cell homeostasis, is responsible for cellular waste degradation. Modulating autophagic flux is a strategy to remove damaging cell waste. In this study, CysLTR1 antagonist application was shown to increase autophagic flux. Furthermore, inhibition of CysLTR1 resulted in decreased levels of autophagosomes, late endosomes/lysosomes, aggregated proteins, and reactive oxygen species (ROS) in ARPE-19 cells.
SCIENTIFIC REPORTS
(2023)
Article
Environmental Sciences
Xiangjing Meng, Sumei Guo, Xiaoxia Zhang, Bo Jiao, Xiaohan Yang, Ming Li, Chao Li, Jin He, Shangya Chen, Cheng Peng, Hua Shao, Qiang Jia
Summary: Inhibition of HMGB1 has a positive effect in alleviating TDI-induced asthma by activating the ROS/AMPK/autophagy pathway.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Multidisciplinary Sciences
Ricardo Louzada da Silva, Diana M. Elizondo, Nailah Z. D. Brandy, Naomi L. Haddock, Thomas A. Boddie, Lais Lima de Oliveira, Amelia Ribeiro de Jesus, Roque Pacheco de Almeida, Tatiana Rodrigues de Moura, Michael W. Lipscomb
Summary: The study revealed that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses during infection, leading to increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, while inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. This highlights AIF1 as a critical regulatory component in governing monocyte and macrophage immune functions during parasitic infections and demonstrates how the parasite can suppress this gene as an immune evasion tactic.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Nicole Blaquiere, Georgette M. Castanedo, Jason D. Burch, Leonid M. Berezhkovskiy, Hans Brightbill, Suzanne Brown, Connie Chan, Po-Chang Chiang, James J. Crawford, Teresa Dong, Peter Fan, Jianwen Feng, Nico Ghilardi, Robert Godemann, Emily Gogol, Alice Grabbe, Alison J. Hole, Baihua Hu, Sarah G. Hymowitz, Moulay Hicham Alaoui Ismaili, Hoa Le, Patrick Lee, Wyne Lee, Xingyu Lin, Ning Liu, Paul A. McEwan, Brent McKenzie, Hernani L. Silvestre, Eric Suto, Swathi Sujatha-Bhaskar, Guosheng Wu, Lawren C. Wu, Yamin Zhang, Zoe Zhong, Steven T. Staben
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
James J. y Crawford, Adam R. Johnson, Dinah L. Misner, Lisa D. Belmont, Georgette Castanedo, Regina Choy, Melis Coraggio, Liming Doug, Charles Eigenbrot, Rebecca Erickson, Nico Ghilardi, Jonathan Hau, Arna Katewa, Pawan Bir Kohli, Wendy Lee, Joseph W. Lubach, Brent S. McKenzie, Daniel F. Ortwine, Leah Schutt, Suzanne Tay, BinQing Wei, Karin Reif, Lichuan Liu, Harvey Wong, Wendy B. Young
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Hans D. Brightbill, Eric Suto, Nicole Blaquiere, Nandhini Ramamoorthi, Swathi Sujatha-Bhaskar, Emily B. Gogol, Georgette M. Castanedo, Benjamin T. Jackson, Youngsu C. Kwon, Susan Haller, Justin Lesch, Karin Bents, Christine Everett, Pawan Bir Kohli, Sandra Linge, Laura Christian, Kathy Barrett, Allan Jaochico, Leonid M. Berezhkovskiy, Peter W. Fan, Zora Modrusan, Kelli Veliz, Michael J. Townsend, Jason DeVoss, Adam R. Johnson, Robert Godemann, Wyne P. Lee, Cary D. Austin, Brent S. McKenzie, Jason A. Hackney, James J. Crawford, Steven T. Staben, Moulay H. Alaoui Ismaili, Lawren C. Wu, Nico Ghilardi
NATURE COMMUNICATIONS
(2018)
Article
Immunology
Brian C. Miller, Debattama R. Sen, Rose Al Abosy, Kevin Bi, Yamini V. Virkud, Martin W. LaFleur, Kathleen B. Yates, Ana Lako, Kristen Felt, Girish S. Naik, Michael Manos, Evisa Gjini, Juhi R. Kuchroo, Jeffrey J. Ishizuka, Jenna L. Collier, Gabriel K. Griffin, Seth Maleri, Dawn E. Comstock, Sarah A. Weiss, Flavian D. Brown, Arpit Panda, Margaret D. Zimmer, Robert T. Manguso, F. Stephen Hodi, Scott J. Rodig, Arlene H. Sharpe, W. Nicholas Haining
Article
Chemistry, Medicinal
Mark Zak, Emily J. Hanan, Patrick Lupardus, David G. Brown, Colin Robinson, Michael Siu, Joseph P. Lyssikatos, F. Anthony Romero, Guiling Zhao, Terry Kellar, Rohan Mendonca, Nicholas C. Ray, Simon C. Goodacre, Peter H. Crackett, Neville McLean, Christopher A. Hurley, Po-wai Yuen, Yun-Xing Cheng, Xiongcai Liu, Marya Liimatta, Pawan Bir Kohli, Jim Nonomiya, Gary Salmon, Gerry Buckley, Julia Lloyd, Paul Gibbons, Nico Ghilardi, Jane R. Kenny, Adam Johnson
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2019)
Review
Immunology
Nico Ghilardi, Rajita Pappu, Joseph R. Arron, Andrew C. Chan
ANNUAL REVIEW OF IMMUNOLOGY, VOL 38
(2020)
Review
Pharmacology & Pharmacy
David F. Choy, Joseph R. Arron
EXPERT OPINION ON THERAPEUTIC TARGETS
(2020)
Article
Biochemistry & Molecular Biology
Cesar A. Corzo, Eugene Varfolomeev, A. Francesca Setiadi, Ross Francis, Sha Klabunde, Kate Senger, Swathi Sujatha-Bhaskar, Joy Drobnick, Steven Do, Eric Suto, Zhiyu Huang, Jeffrey Eastham-Anderson, Arna Katewa, Jodie Pang, Melanie Domeyer, Christopher Dela Cruz, Andres Paler-Martinez, Vivian W. C. Lau, Azadeh Hadadianpour, Vladimir Ramirez-Carrozi, Yonglian Sun, Katherine Bao, Daqi Xu, Emily Hunley, Hans D. Brightbill, Soren Warming, Merone Roose-Girma, Alfred Wong, Lucinda Tam, Claire L. Emson, James J. Crawford, Wendy B. Young, Rajita Pappu, Brent S. McKenzie, Vida Asghari, Domagoj Vucic, Jason A. Hackney, Cary D. Austin, Wyne P. Lee, Annemarie Lekkerkerker, Nico Ghilardi, Marian C. Bryan, James R. Kiefer, Michael J. Townsend, Ali A. Zarrin
Article
Dermatology
Yuan-Hsin Lo, Chi-Shan Li, Hung-Lin Chen, Cho-Ying Chiang, Chi-Chun Huang, Ting-Jui Tu, Tzu-Han Lo, David F. Choy, Joseph R. Arron, Huan-Yuan Chen, Fu-Tong Liu
Summary: The study demonstrates the upregulation of galectin-8 in psoriatic skin lesions and mouse models of psoriasis. Knocking out galectin-8 leads to reduced keratinocyte proliferation and delayed cell cycle progression. Galectin-8 interacts with alpha-tubulin to maintain centrosome integrity, facilitating keratinocyte hyperproliferation in psoriasis.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Medicine, Research & Experimental
Daryle J. DePianto, Jason A. Vander Heiden, Katrina B. Morshead, Kai-Hui Sun, Zora Modrusan, Grace Teng, Paul J. Wolters, Joseph R. Arron
Summary: The compromised regenerative capacity of lung epithelial cells can lead to cellular senescence, which may contribute to fibrosis. Senescent cells with the marker p16 are predominantly located in bronchiolized epithelial structures in scarred regions of IPF and SSc-ILD lung tissue, overlapping with basal epithelial markers Keratin 5 and Keratin 17. These senescent basal epithelial cells in ILD show gene expression patterns similar to terminally differentiating cells in stratified epithelia, driven by p53 activation as part of the senescence program.
Review
Immunology
Jenna L. Collier, Sarah A. Weiss, Kristen E. Pauken, Debattama R. Sen, Arlene H. Sharpe
Summary: CD8(+) T cells play critical roles in infection, cancer, and autoimmunity, but may exhibit dysfunction in different contexts. In cancer and chronic infections, CD8(+) T cells can become exhausted, while in autoimmunity, they retain the ability to cause host tissue damage.
Article
Multidisciplinary Sciences
Seoyeon Lee, Mohammad Naimul Islam, Kaveh Boostanpour, Dvir Aran, Guangchun Jin, Stephanie Christenson, Michael A. Matthay, Walter L. Eckalbar, Daryle J. DePianto, Joseph R. Arron, Liam Magee, Sunita Bhattacharya, Rei Matsumoto, Masaru Kubota, Donna L. Farber, Jahar Bhattacharya, Paul J. Wolters, Mallar Bhattacharya
Summary: Analysis of lung samples from healthy human donors reveals an increase in cellular senescence and pro-fibrotic pathway activation with age. Telomere shortening, decreased lung epithelial cells, and increased fibroblasts are associated with aging. This study shows a profile of increased vulnerability to lung diseases with age, highlighting the importance of genomic analysis and live lung imaging in understanding the natural history of human lung aging.
NATURE COMMUNICATIONS
(2021)
Article
Critical Care Medicine
P. Jane McDowell, John Busby, Catherine E. Hanratty, Ratko Djukanovic, Ashley Woodcock, Samantha Walker, Timothy Colin Hardman, Joseph R. Arron, David F. Choy, Peter Bradding, Chris E. Brightling, Rekha Chaudhuri, Douglas Cowan, Adel H. Mansur, Stephen J. Fowler, Sarah E. Diver, Peter Howarth, James Lordan, Andrew Menzies-Gow, Timothy Harrison, Douglas S. Robinson, Cecile T. J. Holweg, John G. Matthews, Ian D. Pavord, Liam G. Heaney
Summary: This study examined the differences between T2-low and T2-high asthma during exacerbation and found that they are physiologically and symptomatically similar during exacerbation. It also discovered that the inflammatory phenotype of T2-low asthma may be dynamic between stable and exacerbation states. The findings emphasize the importance of understanding the mechanisms of non-T2 asthma.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Immunology
Jenna L. Collier, Kristen E. Pauken, Catherine A. A. Lee, Dillon G. Patterson, Samuel C. Markson, Thomas S. Conway, Megan E. Fung, Joshua A. France, Kyla N. Mucciarone, Christine G. Lian, George F. Murphy, Arlene H. Sharpe
Summary: The authors identify unique features of diabetogenic T cells in the pancreas and peripheral tissues between anti-PD-1-induced type 1 diabetes (T1D) and spontaneous T1D in non-obese diabetic mice, and provide a rationale for monitoring immune-related adverse events in the blood.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Immunology
Mary E. Keir, Tangsheng Yi, Timothy T. Lu, Nico Ghilardi
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)