Article
Biochemistry & Molecular Biology
Frederic V. Schwabe, Lotta Happonen, Sofie Ekestubbe, Ariane Neumann
Summary: This study investigated the effects of LL-37 and LTF on blood-derived CD14(+) monocytes and found that these HDPs can induce the release of TNF alpha, nucleosomes, and monocyte ETs. The formation of ETs by LL-37 is dependent on SOCE, MAPK, and ERK1/2, while the release of ETs by LTF is not affected by any inhibitors used in this study.
Article
Respiratory System
Shumin Liao, Yanhong Huang, Jinxiu Zhang, Qinglan Xiong, Mengshi Chi, Liang Yang, Junhang Zhang, Liang Li, Yunping Fan
Summary: Through clinical observation and laboratory experiments, the study found a relationship between vitamin D deficiency and chronic rhinosinusitis, and vitamin D can promote epithelial tissue repair and enhance host defense responses against viral infections like influenza and bacterial infections like Staphylococcus aureus.
RESPIRATORY RESEARCH
(2023)
Article
Cell Biology
Huidan Zhang, Junai Zhen, Rong Zhang, Yangke Wanyan, Kehang Liu, Xueli Yuan, Liping Tao, Yuqing Chen
Summary: The study found that hCAP18/LL-37 promotes the proliferation of HCC cells through stimulation of the EGFR/HER2/Akt signals and may suppress the antitumor activity of 1,25(OH)(2)D-3 in HCC xenograft tumors. These findings highlight the importance of hCAP18/LL-37 in HCC.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Xubiao Wei, Lulu Zhang, Yinlong Yang, Yanfei Hou, Yifang Xu, Zhimeng Wang, Huili Su, Fangping Han, Jing Han, Peiyuan Liu, Shuiqing Hu, Matthew D. Koci, Xuxu Sun, Conggang Zhang
Summary: LL-37 acts as a transporter for cGAMP, delivering it into target cells to activate the immune response. cGAMP transferred by LL-37 enhances antiviral immunity and inducers such as vitamin D-3 and sodium butyrate enhance LL-37 expression, further strengthening the immune response.
Article
Pediatrics
Shaojie Zhao, Yixiu He, Menglan Pan, Bingzhang Chen, Siqi Zhang, Yufeng Zhang, Yafei Zhu
Summary: Vitamin D deficiency is associated with the occurrence and severity of bacterial pneumonia in infants. The level of LL-37 is increased in infants with bacterial pneumonia but decreases with disease progression.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Ferenc Zsila, Maria Ricci, Imola Csilla Szigyarto, Priyanka Singh, Tamas Beke-Somfai
Summary: Host defense antimicrobial peptides (HDPs) play a crucial role in the innate immune system, with nonspecific activity against a broad spectrum of microorganisms. These peptides also have diverse biological functions in wound healing, angiogenesis, and immunomodulation. Additionally, they exhibit high affinity to interact with human lipid signaling molecules and influence bacterial communication systems like quorum sensing (QS).
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ivan V. Bogdanov, Maria A. Streltsova, Elena I. Kovalenko, Alexander M. Sapozhnikov, Pavel V. Panteleev, Tatiana V. Ovchinnikova
Summary: LL-37 is a human defense antimicrobial peptide that exhibits antimicrobial activities and can induce cytokine production. However, its physiological relevance and absorption in the gut remains unclear.
Article
Biochemical Research Methods
William F. Porto, Sergio A. Alencar
Summary: Cathelicidin antimicrobial peptides, including LL-37, are important host defense peptides with various activities. We investigated the effects of single nucleotide polymorphism (SNP)-driven point mutations on LL-37 structure and activity. Our results suggest that while the mutations had minimal impact on LL-37 activity, some mutations could reduce its antimicrobial activity and alter its structure.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2023)
Article
Immunology
Geysson Javier Fernandez, Julieta M. Ramirez-Mejia, Jorge Andres Castillo, Silvio Urcuqui-Inchima
Summary: Although there is no vaccine or effective treatment for Zika virus (ZIKV), vitamin D has been found to restrict ZIKV infection in macrophages by altering gene expression and inducing antimicrobial peptide expression. This study highlights the potential of vitamin D-inducible peptides as an antiviral treatment for Zika fever.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Debabrata Biswas, Poornima Ambalavanan, Miriam Ravins, Aparna Anand, Abhinay Sharma, Kimberly Xuan Zhen Lim, Rachel Ying Min Tan, Hwee Ying Lim, Asaf Sol, Gilad Bachrach, Veronique Angeli, Emanuel Hanski
Summary: Research has shown that Group A Streptococcus can resist host immune responses by cleaving the host's antimicrobial peptide LL-37, leading to soft-tissue infections. Furthermore, the activation of host receptors mediated by LL-37 is critical for defense against GAS infections.
Article
Gastroenterology & Hepatology
Banglao Xu, Xianan Wu, Yi Gong, Ju Cao
Summary: IL-27 can be involved in host immunity against Clostridioides difficile infection by induction of LL-37/CRAMP. Therefore, the IL-27-LL-37 axis may be a valuable pathway in the development of immune-based therapy.
Article
Cell Biology
Xue-Kun Guo, Jiali Wang, Vincent P. van Hensbergen, Jintao Liu, Huji Xu, Xiaoyu Hu
Summary: This study reveals a unique pattern of crypt occupation by mucus-associated biofilms during early colitis, which is genetically dependent on bacterial biofilm-forming capacity and restricted by host epithelial O 1,2-fucosylation. Deficiency in O 1,2-fucosylation leads to increased crypt occupation by biofilms and exacerbated intestinal inflammation. Mechanistically, fucose from biofilm-occupied mucus suppresses biofilm formation and related genes. Additionally, fucose administration ameliorates experimental colitis, suggesting the therapeutic potential of fucose for biofilm-related disorders.
Review
Biochemistry & Molecular Biology
Alfonso Rodriguez-Gil, Estrella Carrillo-Cruz, Cristina Marrero-Cepeda, Guillermo Rodriguez, Jose A. Perez-Simon
Summary: Vitamin D plays a dual role in the immune system and tumor cells, potentially decreasing graft-versus-host disease and relapse rates.
Article
Multidisciplinary Sciences
Matthias Keutmann, Gabriele Hermes, Denise Meinberger, Annika Roth, Jannik Stemler, Oliver A. Cornely, Andreas R. Klatt, Thomas Streichert
Summary: Several studies have discussed the beneficial effects of vitamin D on COVID-19 progression. Vitamin D stimulates the expression of the antimicrobial peptide LL-37, which has been shown to antagonize SARS-CoV-2. This study investigated the association between LL-37 and vitamin D serum levels and the severity of COVID-19. The findings suggest that the LL-37/leukocyte count ratio could be used as an indicator to assess the risk of COVID-19 progression at an early stage.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Yan Zhou, Yali Qiu, Wuping Bao, Lei Han, Yishu Xue, Yingying Zhang, Xue Tian, Qiang Fu, Chengjian Lv, Dongning Yin, Min Zhang
Summary: This study investigates the influence of vitamin D on patients with T2-high and T2-low asthma. The results show that asthma patients have decreased vitamin D levels, and vitamin D deficiency can exacerbate asthma symptoms. Vitamin D levels are associated with asthma severity, especially in T2-low asthma. Further research is needed to understand the mechanisms of vitamin D on different types of asthma.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biology
Janna C. Nawroth, Anne M. van der Does, Amy Ryan (Firth), Eva Kanso
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2020)
Review
Immunology
Jasmijn A. Schrumpf, Anne M. van der Does, Pieter S. Hiemstra
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Physiology
Sander van Riet, Annemarie van Schadewijk, P. Padmini S. J. Khedoe, Ronald W. A. L. Limpens, Montserrat Barcena, Jan Stolk, Pieter S. Hiemstra, Anne M. van der Does
Summary: The development of effective treatment strategies for lung tissue destruction, such as emphysema, would greatly benefit from representative human in vitro models of the alveolar compartment. Studying the effect of cellular cross talk and biomechanical cues on alveolar epithelial function can provide new insight for tissue repair strategies. This study successfully demonstrated the feasibility of using patient-derived alveolar type 2 cells (AEC2s) in microfluidic chip cultures to develop more representative human preclinical models of the diseased alveolar compartment.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Immunology
Anna H. E. Roukens, Cilia R. Pothast, Marion Koenig, Wesley Huisman, Tim Dalebout, Tamar Tak, Shohreh Azimi, Yvonne Kruize, Renate S. Hagedoorn, Mihaela Zlei, Frank J. T. Staal, Fenna J. de Bie, Jacques J. M. van Dongen, Sesmu M. Arbous, Jaimie L. H. Zhang, Maaike Verheij, Corine Prins, Anne M. van der Does, Pieter S. Hiemstra, Jutte J. C. de Vries, Jacqueline J. Janse, Meta Roestenberg, Sebenzile K. Myeni, Marjolein Kikkert, Maria Yazdanbakhsh, Mirjam H. M. Heemskerk, Hermelijn H. Smits, Simon P. Jochems
Summary: Systemic immune cell dynamics during COVID-19 have been well-documented, but less is known about immune cells in the respiratory tract. This study characterized nasal and systemic immune cells in COVID-19 patients, showing increased inflammatory cells in the nasal mucosa during acute infection. After recovery, nasal immune cells mostly normalized, but SARS-CoV-2-specific CD8(+) T cells could persist for at least 2 months.
Review
Respiratory System
Amy M. de Waal, Pieter S. Hiemstra, Tom H. M. Ottenhoff, Simone A. Joosten, Anne M. van der Does
Summary: The lung epithelium plays a crucial role in tuberculosis disease, acting as a barrier to Mycobacterium tuberculosis and responding to infection by producing immune mediators. The interactions between epithelial cells, immune cells, and Mtb are important for understanding the early events of Mtb infection.
Article
Nutrition & Dietetics
Rachida Rafiq, Floor E. Aleva, Jasmijn A. Schrumpf, Johannes M. Daniels, Pierre M. Bet, Wim G. Boersma, Paul Bresser, Michiel Spanbroek, Paul Lips, Tim J. van den Broek, Bart J. F. Keijser, Andre J. A. M. van der Ven, Pieter S. Hiemstra, Martin den Heijer, Renate T. de Jongh
Summary: This study assessed the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. The results showed that vitamin D supplementation did not affect the exacerbation rate in COPD patients.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Multidisciplinary Sciences
Dennis K. Ninaber, Anne M. van der Does, Pieter S. Hiemstra
Summary: The airway epithelial cell layer is constantly exposed to inhaled substances and plays a central role in lung diseases. In vitro epithelial culture models offer a controlled environment for studying the role of epithelium in pathogenesis and therapy. This manuscript provides a robust protocol for isolating and culturing airway epithelial cells, along with characterization and various applications of these cultures.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Health Care Sciences & Services
Nadia Baalbaki, Jelle M. Blankestijn, Mahmoud I. Abdel-Aziz, Jan de Backer, Somayeh Bazdar, Ines Beekers, Rosanne J. H. C. G. Beijers, Joop P. van den Bergh, Lizan D. Bloemsma, Harm Jan Bogaard, Job J. M. H. van Bragt, Vera van den Brink, Jean Paul Charbonnier, Merel E. B. Cornelissen, Yennece Dagelet, Elin Haf Davies, Anne M. van der Does, George S. Downward, Cornelis M. van Drunen, Debbie Gach, J. J. Miranda Geelhoed, Jorrit Glastra, Kornel Golebski, Irene H. Heijink, Judith C. S. Holtjer, Sebastiaan Holverda, Laura Houweling, John J. L. Jacobs, Renee Jonker, Renate Kos, Ramon C. J. Langen, Ivo van der Lee, Asabi Leliveld, Firdaus A. A. Mohamed Hoesein, Anne H. Neerincx, Lieke Noij, Johan Olsson, Marianne van de Pol, Simon D. Pouwels, Emiel Rolink, Michael Rutgers, Havva Sahin, Daphne Schaminee, Annemie M. W. J. Schols, Lisanne Schuurman, Gitte Slingers, Olie Smeenk, Brigitte Sondermeijer, Paul J. Skipp, Marisca Tamarit, Inge Verkouter, Roel Vermeulen, Rianne de Vries, Els J. M. Weersink, Marco van de Werken, Yolanda de Wit-van Wijck, Stewart Young, Esther J. Nossent, Anke H. van der Zee
Summary: The P4O2 COVID-19 study aims to identify long COVID patients at risk for developing chronic lung disease and to find personalized therapeutic strategies. The study showed persistent symptoms and abnormalities in post-COVID patients, with the most commonly reported symptoms being respiratory and neurological symptoms.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Engineering, Biomedical
Janna C. Nawroth, Doris Roth, Annemarie van Schadewijk, Abilash Ravi, Tengku Ibrahim Maulana, Christiana N. Senger, Sander van Riet, Dennis K. Ninaber, Amy M. de Waal, Dorothea Kraft, Pieter S. Hiemstra, Amy L. Ryan, Anne M. van der Does
Summary: We develop an advanced organ-on-chip device to study the influence of dynamic cues, such as medium and airflow, on human airway epithelial cell differentiation and maturation. By applying airflow and stretch to the airway chip, we observe increased polarization of mucociliary clearance, reduced inflammatory protein secretion, and decreased gene expression of matrix metalloproteinase (MMP) 9 and other extracellular matrix factors. These findings highlight the importance of breathing-like mechanical stimuli in airway epithelial biology and suggest the potential use of this model for studying specific epithelial pathologies.
MATERIALS TODAY BIO
(2023)
Article
Immunology
Melissa Thaler, Ying Wang, Anne M. van der Does, Alen Faiz, Dennis K. Ninaber, Natacha S. Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J. Snijder, Peter J. Bredenbeek, Pieter S. Hiemstra, Martijn J. van Hemert
Summary: The consequences of SARS-CoV-2 infection can range from asymptomatic to fatal disease, and the susceptibility to infection varies depending on the different regions of the respiratory tract. The cellular composition and differentiation of the epithelial cells play a role in the infection process.
JOURNAL OF INNATE IMMUNITY
(2023)
Article
Immunology
Melissa Thaler, Ying Wang, Anne M. van der Does, Alen Faiz, Dennis K. Ninaber, Natacha S. Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J. Snijder, Peter J. Bredenbeek, Pieter S. Hiemstra, Martijn J. van Hemert
Summary: The cellular biology underlying the variations in epithelial susceptibility to SARS-CoV-2 infection in different anatomical locations of the respiratory tract is not completely understood. This study used air-liquid interface cultures of primary human tracheal and bronchial epithelial cells to investigate the impact of cellular composition and differentiation on SARS-CoV-2 infection. The results showed that SARS-CoV-2 primarily infected ciliated cells, goblet cells, and transient secretory cells. The viral replication was influenced by differences in cellular composition, especially the percentage of ciliated cells. Moreover, the study found that the differentiation time affected the cell entry factors. These findings provide insights into the variable susceptibility to SARS-CoV-2 infection between individuals and anatomical locations in the respiratory tract.
JOURNAL OF INNATE IMMUNITY
(2023)
Article
Respiratory System
Anne M. van der Does, Rashad M. Mahbub, Dennis K. Ninaber, Senani N. H. Rathnayake, Wim Timens, Maarten van den Berge, Hananeh Aliee, Fabian J. Theis, Martijn C. Nawijn, Pieter S. Hiemstra, Alen Faiz
Summary: This study investigates the early transcriptomic responses of airway epithelial cells to cigarette smoke exposure and compares them to human studies. The results show that oxidative stress, xenobiotic metabolism, immediate early gene expression, and pro-inflammatory pathways are activated early after exposure, followed by an increase in ferroptosis-related cell death pathways at 24 hours. Importantly, the findings of this study align with in-vivo human studies and validate the use of ALI-PBEC cultures to study lung epithelial response to inhaled toxicants.
RESPIRATORY RESEARCH
(2022)
