Review
Biochemistry & Molecular Biology
Yu Chen, Yuzhen Ouyang, Zhixin Li, Xiufang Wang, Jian Ma
Summary: S100A8 and S100A9, as Ca2+ binding proteins in the S100 family, have crucial roles in modulating inflammatory responses and inflammation-associated diseases. They participate in multiple signaling pathways in tumor cells and contribute to tumor development, growth, and metastasis. Moreover, they have shown potential as diagnostic or prognostic biomarkers in cancer and have become therapeutic targets. This review focuses on the characteristics of S100A8/A9, S100A9, and S100A8, their interactions with tumor cells and microenvironments, and their clinical applications as biomarkers and therapeutic targets.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Immunology
Jose Inciarte-Mundo, Beatriz Frade-Sosa, Raimon Sanmarti
Summary: S100A9/S100A8 (calprotectin), a member of the S100 protein family, plays a crucial role in innate immunity activation and is essential in the pathogenesis of rheumatoid arthritis (RA). Calprotectin levels in serum or plasma have been found to correlate better with composite inflammatory disease activity indexes compared to conventional markers like C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). It independently predicts radiographic progression and shows strong correlations with other sensitive techniques to detect inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Joan Defrene, Sofiane Berrazouane, Nayeli Esparza, Nathalie Page, Marie-France Cote, Stephane Gobeil, Fawzi Aoudjit, Philippe A. Tessier
Summary: The study explored the role of S100A8 and S100A9 in psoriasis-associated skin hyperplasia and immune responses, revealing that they regulate psoriasis by inhibiting the production of IL-17A and -F. The findings provide new insights into the biological functions of S100A8 and S100A9 in psoriasis pathogenesis.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Rheumatology
Liliana F. Mellor, Nuria Gago-Lopez, Latifa Bakiri, Felix N. Schmidt, Bjorn Busse, Simon Rauber, Maria Jimenez, Diego Megias, Sergio Oterino-Soto, Ricardo Sanchez-Prieto, Sergei Grivennikov, Xinzhu Pu, Julia Oxford, Andreas Ramming, Georg Schett, Erwin F. Wagner
Summary: Keratinocyte-derived S100A9 plays a regulatory role in psoriatic skin and joint disease. In addition, S100A9 and CP have the potential to serve as biomarkers for identifying Ps patients at risk of developing PsA.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Immunology
Ning Yu, Chen Peng, Wenjuan Chen, Ziwen Sun, Jianfeng Zheng, Shujie Zhang, Yangfeng Ding, Yuling Shi
Summary: In generalized pustular psoriasis (GPP), decreased serum amino acids inhibit the immune response of blood monocytes through regulating the release of IL-1 beta, serving as a feedback mechanism to prevent excessive inflammation in GPP.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Alexander Moeller, Saskia-Larissa Jauch-Speer, Shrey Gandhi, Thomas Vogl, Johannes Roth, Olesja Fehler
Summary: The S100A8/A9 heterocomplex is a widely expressed damage-associated molecular pattern, and it interacts with various receptors including TLR4, RAGE, CD33, CD68, CD69, and CD147. However, the exact mode of action and which receptors are involved in the inflammatory response of myeloid immune cells are still unclear. In this study, the authors used CRISPR/Cas9 to delete CD33, CD68, CD69, and CD147 in ER-Hoxb8 monocytes and compared their response to S100A8 and S100A9 with TLR4 knockout monocytes. The results showed that TLR4 is the dominant receptor for the S100-induced inflammatory activation of monocytes.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Farnaz Razmkhah, Sena Kim, Sora Lim, Abdul-Jalil Dania, Jaebok Choi
Summary: S100A8 and S100A9 can initiate various signaling pathways and modulate cell function both inside and outside immune cells. They have been reported as dysregulated genes and proteins in various cancers, including hematologic malignancies. In this review, we discuss their critical roles in forming and promoting the malignant bone marrow microenvironment, as well as their potential as biomarkers and therapeutic targets in hematologic malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Allergy
Patrick Baum, Sudha Visvanathan, Sandra Garcet, Janine Roy, Ramona Schmid, Sebastian Bossert, Benjamin Lang, Herve Bachelez, Robert Bissonnette, Christian Thoma, James G. Krueger
Summary: This study revealed that the IL-36 pathway plays a significant role in the pathogenesis of generalized pustular psoriasis. Treatment with spesolimab, an anti-IL-36 receptor antibody, resulted in rapid improvement of skin and pustular symptoms in patients with GPP. The treatment also modulated dysregulated molecular pathways associated with GPP and PPP, leading to improved clinical outcomes.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Wei-Chih Liao, Chih-Ta Chen, You-Shu Tsai, Xin-Ya Wang, Yen-Tzu Chang, Ming-Shiang Wu, Lu-Ping Chow
Summary: Background: Cancer cachexia is a common syndrome in pancreatic cancer patients, characterized by weight loss and muscle wasting. Through bioinformatic analysis, we identified potential pro-inflammatory factors associated with cachexia and investigated their ability to induce muscle atrophy. The expression levels of these factors were significantly elevated in tumors and serum of patients with cachexia compared to those without. Serum levels of these factors were positively correlated with weight loss and could independently predict the occurrence of cachexia.
Article
Dermatology
Claire Q. Wang, Sokol Haxhinasto, Sandra Garcet, Norma Kunjravia, Inna Cueto, Juana Gonzalez, Darshna Rambhia, Olivier Harari, Matthew A. Sleeman, Jennifer D. Hamilton, Wei Keat Lim, Jan Freudenberg, George D. Kalliolias, Paresh Thakker, Robert Bissonnette, James G. Krueger
Summary: Palmoplantar pustular psoriasis (PPPP) and non-pustular palmoplantar psoriasis (NPPP) are localized, debilitating forms of psoriasis. This study found that NPPP shows more pronounced T helper 1-mediated inflammation, while PPPP exhibits stronger neutrophil-associated activity.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Ruisheng Song, Kevin Struhl
Summary: The study reveals that the calcium-dependent cytokines S100A8 and S100A9 can act as transcriptional coactivators in breast cellular transformation, enhancing oncogenic transcription and promoting the transformation phenotype.
Review
Immunology
Ranjitha Uppala, Lam C. Tsoi, Paul W. Harms, Bo Wang, Allison C. Billi, Emanual Maverakis, J. Michelle Kahlenberg, Nicole L. Ward, Johann E. Gudjonsson
Summary: Psoriasis is a chronic inflammatory skin condition with a wide range of clinical manifestations. Genetic studies have identified six genetic variants predisposing to pustular psoriasis, with IL-36 cytokines playing a central role in disease pathophysiology.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
H. Bachelez, S-E Choon, S. Marrakchi, A. D. Burden, T-F Tsai, A. Morita, A. A. Navarini, M. Zheng, J. Xu, H. Turki, M. J. Anadkat, S. Rajeswari, H. Hua, S. D. Vulcu, D. Hall, K. Tetzlaff, C. Thoma, M. G. Lebwohl
Summary: In a phase 2 randomized trial, spesolimab, an interleukin-36 receptor inhibitor, showed a higher rate of lesion clearance in GPP patients compared to placebo, but was associated with risks of infections and systemic drug reactions. Further longer and larger trials are needed to assess the efficacy and safety of spesolimab in patients with pustular psoriasis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Giovanni Genovese, Chiara Moltrasio, Nicoletta Cassano, Carlo Alberto Maronese, Gino Antonio Vena, Angelo Valerio Marzano
Summary: Pustular psoriasis is a clinicopathological entity with different variants characterized by sterile pustules on an erythematous base, showing intense inflammatory response and involvement of the IL-36 axis. Due to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited, leading to ongoing debates on the diagnosis and treatment of PP.
Article
Chemistry, Multidisciplinary
Antonella Russo, Hendrik Schuermann, Matthias Brandt, Katja Scholz, Anna Livia L. Matos, David Grill, Julian Revenstorff, Max Rembrink, Meike von Wulffen, Lena Fischer-Riepe, Peter J. Hanley, Hans Haecker, Monika Pruenster, Francisco Sanchez-Madrid, Sven Hermann, Luisa Klotz, Volker Gerke, Timo Betz, Thomas Vogl, Johannes Roth
Summary: It has been demonstrated that S100A8/S100A9 tetramers can weaken the inflammatory response of leukocytes in vitro and in vivo, and this is mediated by the interaction between S100A8/S100A9 tetramers and CD69, rather than the binding of S100A8/S100A9 dimers to TLR4. These findings reveal the important role of the quaternary structure of S100 proteins in regulating leukocyte inflammatory responses.
Letter
Dermatology
Fuminori Katsumata, Koji Kamiya, Hirofumi Okada, Takeo Maekawa, Mayumi Komine, Mamitaro Ohtsuki
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
Hiroki Yamamoto, Koji Kamiya, Hirofumi Okada, Takeo Maekawa, Mayumi Komine, Mamitaro Ohtsuki
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki, Mayumi Komine
Summary: This study investigated the role of IL-33 in normal human epidermal keratinocytes (NHEKs) by utilizing RNA interference to knock down cellular IL-33. The results showed that IL-33 knockdown affected cell division and motility, possibly by attenuating ECT2 expression and slightly decreasing RhoA activity.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Letter
Dermatology
Okuto Iwasawa, Koji Kamiya, Hirofumi Okada, Mayumi Komine, Mamitaro Ohtsuki
JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
Okuto Iwasawa, Koji Kamiya, Mayumi Komine, Mamitaro Ohtsuki
JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
Megumi Kishimoto, Mayumi Komine, Koji Kamiya, Junichi Sugai, Aya Kuwahara, Naoki Morimoto, Mamitaro Ohtsuki
JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
Ryuzo Ichimura, Koji Kamiya, Mayumi Komine, Meijuan Jin, Hitomi Miyauchi, Takeo Maekawa, Mio Sakaguchi, Kentaro Tsuji, Hirotoshi Kawata, Mamitaro Ohtsuki
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
Okuto Iwasawa, Koji Kamiya, Hirofumi Okada, Takeo Maekawa, Mayumi Komine, Mamitaro Ohtsuki
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2023)
Letter
Dermatology
Yuichi Toyama, Koji Kamiya, Takeo Maekawa, Mayumi Komine, Mamitaro Ohtsuki
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Suphagan Boonpethkaew, Jitlada Meephansan, Onjira Jumlongpim, Pattarin Tangtanatakul, Wipasiri Soonthornchai, Jongkonnee Wongpiyabovorn, Ratchanee Vipanurat, Mayumi Komine
Summary: Exploring the transcriptome in the peripheral edge of lesional skin is crucial for understanding the molecules and signaling pathways that contribute to inflammation. The study identified differentially expressed genes in the lesional skin, which enhanced functions related to tissue growth, cell migration, and immune response. The findings suggest that inflammation in the lesional skin may be driven by specific signaling pathways, potentially leading to the discovery of new therapeutic targets for psoriasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Tomoyuki Hioki, Mayumi Komine, Mamitaro Ohtsuki
Summary: Psoriatic arthritis is a chronic inflammatory disorder that can cause deformities and joint damage, impacting quality of life. Early diagnosis and intervention are important to prevent permanent disability, but the clinical features overlap with other diseases, making early detection and intervention challenging.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Tuba M. Ansary, M. D. Razib Hossain, Mayumi Komine, Mamitaro Ohtsuki
Summary: Melanoma and squamous cell carcinoma (SCC) are the most common neoplasms in white people, with increasing incidence rates. SCC, the most prevalent malignancy among nonmelanoma skin cancers, is influenced by factors such as extreme ultraviolet radiation, hereditary predisposition, and immunosuppression. SCC tumors have a high tumor mutational burden and expression of immune checkpoints, making them highly responsive to immunotherapies. However, challenges such as resistance to immunotherapy and difficulty in patient selection exist. This review explores the genetic alterations related to SCC, factors contributing to the benefits of immunotherapy, and challenges associated with this treatment regime.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Mayumi Komine, Tuba Mussarat Ansary, Md Razib Hossain, Koji Kamiya, Mamitaro Ohtsuki
Summary: COVID-19 is a global viral infection caused by SARS-CoV-2, possibly originating from bat coronaviruses in China. Deforestation by humans may have led to host conversion and exposure of wild bats to new environments. SARS-CoV-2 infects cells through two mechanisms, and obesity and diseases like hypertension, diabetes, and pulmonary diseases can result in poor prognosis of COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dermatology
Suphagan Boonpethkaew, Jitlada Meephansan, Onjira Jumlongpim, Sasin Charoensuksira, Pattarin Tangtanatakul, Jongkonnee Wongpiyabovorn, Mayumi Komine
Summary: This study compared the gene profiles in the peripheral edge (PE) and center (CE) of plaques to elucidate the chronological molecular events in plaque formation. Inflammation is likely initiated in the PE, characterized by the presence of specific molecules such as IL-36 alpha, S100A7, and S100A15. The inflammatory state progresses towards a more stable state in the CE, where growth factor activities are increased, potentially leading to the regression of inflammation. These findings contribute to the development of novel therapies for psoriasis.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Letter
Dermatology
Soichiro Kado, Koji Kamiya, Takashi Hosaka, Tetsuya Kawamura, Kenichi Komatsu, Eiji Kajii, Hideyuki Takahashi, Mayumi Komine, Mamitaro Ohtsuki
JOURNAL OF DERMATOLOGY
(2023)