RPEP-04831 · 2020The review connects three bodies of evidence. First, epidemiological data shows vitamin D deficiency is associated with higher risk of streptococcal infections, including pneumonia, meningitis, sepsis, and skin infections.
Second, vitamin D directly stimulates production of antimicrobial peptides, particularly cathelicidin (LL-37) and lactoferrin. These peptides punch holes in bacterial membranes and modulate immune cell behavior.
Third, vitamin D enhances other innate immune functions: phagocytosis (immune cells physically engulfing bacteria) and oxidative burst (production of reactive oxygen species that kill engulfed bacteria). Together, these mechanisms explain why low vitamin D leaves people more vulnerable to streptococcal infections.
Guevara, Miriam A; Lu, Jacky; Moore, Rebecca E; Chambers, Schuyler A; Eastman, Alison J; Francis, Jamisha D; Noble, Kristen N; Doster, Ryan S; Osteen, Kevin G; Damo, Steven M; Manning, Shannon D; Aronoff, David M; Halasa, Natasha B; Townsend, Steven D; Gaddy, Jennifer A · Review
RPEP-04852 · 2020The study overturned a previous assumption. DNA was thought to be the key NET component driving inflammation in psoriasis. Instead, RNA is the critical molecule.
NET-associated RNA (naRNA), when complexed with LL-37, triggered both cytokine release and new NET formation by neutrophils through TLR8 (human) and TLR13 (mouse) receptors. This happened independently of the canonical NET component DNA.
The self-amplifying mechanism: activated neutrophils release NETs containing RNA. That RNA binds LL-37 (abundant in psoriatic skin). The complex activates more neutrophils to release more NETs with more RNA. Each cycle amplifies the inflammation.
Transferring NETs from activated neutrophils to naive (unstimulated) neutrophils triggered additional NET release, directly demonstrating the self-propagating nature of the cycle.
RNA was abundant in NETs and in psoriatic skin but not in healthy skin. This positions naRNA as a physiologically relevant NET component and a driver of chronic psoriatic inflammation.
Herster, Franziska; Bittner, Zsofia; Archer, Nathan K; Dickhöfer, Sabine; Eisel, David; Eigenbrod, Tatjana; Knorpp, Thomas; Schneiderhan-Marra, Nicole; Löffler, Markus W; Kalbacher, Hubert; Vierbuchen, Tim; Heine, Holger; Miller, Lloyd S; Hartl, Dominik; Freund, Lukas; Schäkel, Knut; Heister, Martin; Ghoreschi, Kamran; Weber, Alexander N R · Mechanistic (In Vitro + In Vivo)
RPEP-04960 · 2020ATP synthase inactivation sensitized S. aureus to killing by hBD2, hBD4, LL-37, and histatin 5; resveratrol (an ATP synthase inhibitor) reproduced this sensitization.
Liu, Liping; Beck, Christian; Nøhr-Meldgaard, Katrine; Peschel, Andreas; Kretschmer, Dorothee; Ingmer, Hanne; Vestergaard, Martin · In Vitro
RPEP-04967 · 2020CAMP transgenic mice showed increased Salmonella resistance, restored wound healing in Camp-KO skin, and topical vitamin D induced LL-37 expression with enhanced S. aureus killing in wounds.
Lowry, Malcolm B; Guo, Chunxiao; Zhang, Yang; Fantacone, Mary L; Logan, Isabelle E; Campbell, Yan; Zhang, Weijian; Le, Mai; Indra, Arup K; Ganguli-Indra, Gitali; Xie, Jingwei; Gallo, Richard L; Koeffler, H Phillip; Gombart, Adrian F · Animal
RPEP-04971 · 2020Excess dsDNA fragments triggered psoriasis-like keratinocyte changes; vitamin D blocked this via cathelicidin (CAMP), which was required for the anti-inflammatory effect.
Luo, Y; Hara, T; Kawashima, A; Ishido, Y; Suzuki, S; Ishii, N; Kambara, T; Suzuki, K · In Vitro
RPEP-04977 · 2020LL-37, defensins, S100 proteins, lipocalin 2, and RNase 7 are highly expressed in psoriatic skin and bridge innate and adaptive immune responses in disease pathogenesis.
Ma, Jing-Yi; Shao, Shuai; Wang, Gang · Review
RPEP-04980 · 2020Vaginal AMPs (defensins, LL-37, lactoferrin, SLPI, calprotectin, lysozyme, elafin) provide innate defense against STIs; some (LL-37, magainin 2, nisin) have dual spermicidal-antimicrobial activity.
Madanchi, H; Shoushtari, M; Kashani, H H; Sardari, S · Review
RPEP-04981 · 2020Truncated rCap18 showed superior antimicrobial activity with lower cytotoxicity; truncated hCap18 had better LPS-binding ability; both non-toxic to human fibroblasts at MIC.
Madanchi, Hamid; Ebrahimi Kiasari, Ramin; Seyed Mousavi, Seyed Javad; Johari, Behrooz; Shabani, Ali Akbar; Sardari, Soroush · In Vitro
RPEP-05031 · 2020Antimicrobial peptides LL-37, human beta-defensins, and S100A7 improve tight junction barrier function in addition to their antimicrobial activity, suggesting they could be used for barrier repair in atopic dermatitis.
Nguyen, Hai Le Thanh; Trujillo-Paez, Juan Valentin; Umehara, Yoshie; Yue, Hainan; Peng, Ge; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Song, Pu; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Niyonsaba, François · Review
RPEP-05047 · 2020LL-37 complexed to self-DNA acts as an autoantigen in psoriasis and lupus, activating interferon production by plasmacytoid dendritic cells, while also having dual antiviral and pro-inflammatory roles.
Pahar, Bapi; Madonna, Stefania; Das, Arpita; Albanesi, Cristina; Girolomoni, Giampiero · Review
RPEP-05057 · 2020Linear PEI/pDNA polyplexes successfully transfected human keratinocytes and fibroblasts to overexpress LL-37, with supernatants reducing S. aureus growth by 95.8%.
Patiño Vargas, Maria Isabel; Mesa Cadavid, Mónica; Arenas Gómez, Claudia Marcela; Diosa Arango, Johnatan; Restrepo Múnera, Luz Marina; Becerra Colorado, Natalia Yiset · In Vitro
RPEP-05087 · 2020Low BMI individuals with latent TB had diminished systemic, baseline, and mycobacterial antigen-stimulated levels of HNP1-3, granulysin, HBD-2, and cathelicidin compared to normal BMI counterparts, with positive BMI-AMP correlations.
Rajamanickam, Anuradha; Munisankar, Saravanan; Dolla, Chandra Kumar; Babu, Subash · Observational
RPEP-05097 · 2020Coptis chinensis downregulated KLK5 and cathelicidin expression, inhibited KLK5 protease activity (reducing LL-37 processing), decreased pro-inflammatory cytokines, blocked TLR2/chitin signaling, and inhibited LL-37-induced endothelial cell proliferation.
Roh, Kyung-Baeg; Ryu, De-Hun; Cho, Eunae; Weon, Jin Bae; Park, Deokhoon; Kweon, Dae-Hyuk; Jung, Eunsun · In Vitro
RPEP-05104 · 2020mCRAMP levels were elevated in psoriatic mouse skin and plasma. Psoriatic plasma augmented platelet activation in healthy mouse platelets. The effect was partially mediated through Fpr2/3 (FPR2/ALX), as receptor inhibition or knockout significantly reduced platelet activation.
Salamah, Maryam F; Vallance, Thomas M; Kodji, Xenia; Ravishankar, Divyashree; Williams, Harry F; Brain, Susan D; Vaiyapuri, Sakthivel · Animal Study
RPEP-05284 · 2021Antimicrobial peptide gene expression in skin oscillates along day/night rhythms with two distinct patterns: activity-phase peptides controlled by light and sleep-phase peptides controlled by an internal circadian clock.
Bilska, Bernadetta; Zegar, Aneta; Slominski, Andrzej T; Kleszczyński, Konrad; Cichy, Joanna; Pyza, Elzbieta · Animal
RPEP-05297 · 2021Two short gecko cathelicidin-derived peptides (38-42 and 33-42 fragments) showed potent antioxidant and wound healing activity in mice with significantly lower toxicity than the parent peptide.
Cai, Shasha; Lu, Changao; Liu, Zhenlei; Wang, Wenbo; Lu, Shuxin; Sun, Zhaoxing; Wang, Guannan · Animal
RPEP-05307 · 2021Cathelicidin-MH protected mice from lethal sepsis through a unique combination of antimicrobial activity, LPS neutralization, coagulation suppression (affecting tPA, plasmin, tryptase, elastase, thrombin, and chymase), and MAPK signaling inhibition.
Chai, Jinwei; Chen, Xin; Ye, Tiaofei; Zeng, Baishuang; Zeng, Qingye; Wu, Jiena; Kascakova, Barbora; Martins, Larissa Almeida; Prudnikova, Tatyana; Smatanova, Ivana Kuta; Kotsyfakis, Michail; Xu, Xueqing · Animal
RPEP-05314 · 2021Tiger frog cathelicidin HR-CATH combines direct antimicrobial activity (membrane disruption, DNA degradation) with immune-stimulating properties (macrophage chemotaxis and respiratory burst enhancement).
Chen, Jie; Lin, You-Fu; Chen, Jia-Hao; Chen, Xiang; Lin, Zhi-Hua · In Vitro
RPEP-05339 · 2021Cathelicidin LL37 activates mTORC1 via TLR2, and mTORC1 increases cathelicidin expression, creating a positive feedback loop driving rosacea. Topical rapamycin broke this cycle and improved patient symptoms.
Deng, Zhili; Chen, Mengting; Liu, Yingzi; Xu, San; Ouyang, Yuyan; Shi, Wei; Jian, Dan; Wang, Ben; Liu, Fangfen; Li, Jinmao; Shi, Qian; Peng, Qinqin; Sha, Ke; Xiao, Wenqin; Liu, Tangxiele; Zhang, Yiya; Zhang, Hongbing; Wang, Qian; Sun, Lunquan; Xie, Hongfu; Li, Ji · Animal + Human Observational
RPEP-05350 · 2021CRAMP-deficient mice developed robust skin papillomas after papillomavirus infection while wild-type mice did not. Protection was primarily immune-mediated: CRAMP-deficient mice showed reduced CD4+ and CD8+ T cells and lacked virus-specific neutralizing antibodies.
Dorfer, Sonja; Strasser, Katharina; Reipert, Siegfried; Fischer, Michael B; Shafti-Keramat, Saeed; Bonelli, Michael; Schröckenfuchs, Georg; Bauer, Wolfgang; Kancz, Stefanie; Müller, Lena; Handisurya, Alessandra · Animal
RPEP-05380 · 2021Cathelicidin was ~3x and HBD-2 was >6x higher in BCC patients (p<0.001). Cathelicidin >1,500 pg/mL: OR 9.9 for BCC. HBD-2 >1.2 ng/mL: OR 12.6 for BCC (p<0.001). Both showed high specificity for detecting BCC.
Fijałkowska, Marta; Kowalski, Marek; Koziej, Mateusz; Antoszewski, Bogusław · Case Control
RPEP-05515 · 2021Alanine scanning revealed: some substitutions increased antimicrobial activity, while hydrophobic face substitutions (F5A, I24A, L31A) inhibited scavenger receptor binding and inflammatory response without disrupting RNA organization. LL-37 functions as an "innate immune vetter" via SR-B1 binding.
Kulkarni, Nikhil N; O'Neill, Alan M; Dokoshi, Tatsuya; Luo, Elizabeth W C; Wong, Gerard C L; Gallo, Richard L · In Vitro
RPEP-05664 · 2021LL-37 levels in nasal secretions were inversely associated with multiple measures of bronchiolitis severity. Higher LL-37 meant:
- Shorter hospitalization (rho = -0.340, p = 0.001)
- Less medication use (p = 0.001)
- Shorter oxygen supplementation (rho = -0.339, p = 0.001)
- Shorter IV fluid administration (rho = -0.323, p = 0.001)
These associations remained significant after adjusting for confounding factors like age and other variables.
Notably, serum vitamin D levels were not associated with nasal LL-37 levels, challenging the assumption that vitamin D drives LL-37 production in the airways. Beta-defensin-2 nasal levels also showed no connection to disease severity.
Papadaki, Maria; Marmarinos, Antonios; Tsolia, Maria; Gourgiotis, Dimitrios; Soldatou, Alexandra · Observational
RPEP-05667 · 2021M. restricta and M. globosa activated the NLRP3-ASC inflammasome in human keratinocytes, triggering IL-1β secretion — a key inflammatory signal. All three Malassezia species variably induced the antimicrobial peptides thymic stromal lymphopoietin, β-defensin 2, and LL-37.
Each species created a distinct inflammatory profile: M. sympodialis significantly increased IL-8 and IL-22 protein levels, while M. globosa increased CCL17 mRNA and M. restricta increased CCL22 mRNA. This species-specific pattern of inflammasome activation, cytokine release, and antimicrobial peptide induction suggests that different Malassezia species may drive the distinct clinical presentations of conditions like dandruff versus atopic dermatitis.
Park, Hye Ree; Oh, Jee Hye; Lee, Yu Jin; Park, Song Hee; Lee, Yang Won; Lee, Seongju; Kang, Hoon; Kim, Jung Eun · Basic Research
RPEP-06510 · 2022Injecting vitamin D directly into common warts (verruca vulgaris) significantly increased expression of the antimicrobial peptide LL-37 (cathelicidin) in the skin (p=0.003). Of 20 patients treated, 40% showed complete wart clearance and 35% showed partial response. Warts that cleared completely had the highest LL-37 expression (p=0.022).
After treatment, the skin also showed decreased epidermal thickness and reduced inflammatory cell density, indicating the immune response was shifting from chronic inflammation toward effective viral clearance driven by LL-37.
Sorour, Neveen E; Elesawy, Fatma M; Abdou, Asmaa G; Abdelazeem, Sara E; Akl, Essam M · Interventional Clinical
RPEP-09101 · 2024Both L. salivarius 23-006 and L. paracasei 23-008 reduced skin lesions, skin inflammatory infiltrates, and inflammatory factor expression in the LL-37 rosacea mouse model. The combination of both strains produced the strongest effects.
The probiotics worked by inhibiting the TLR2/MyD88/NF-kB signaling pathway, which is the same pathway LL-37 uses to trigger rosacea inflammation. They also reduced cathelicidin LL-37 expression itself, breaking the cycle. Gut microbiome analysis showed the probiotics increased Lactobacillus levels while reducing Coprococcus and Oscillospira, and strengthened the intestinal barrier.
Postbiotics (the metabolic byproducts of the bacteria, used without live bacteria) also helped but were less effective than live probiotic treatment.
Qi, Xinyue; Xiao, Yiran; Zhang, Xinfeng; Zhu, Zhenlin; Zhang, Hongyan; Wei, Jing; Zhao, Zhixiang; Li, Ji; Chen, Tingtao · Animal Study
RPEP-09130 · 2024The researchers found that the type of organic solvent used during manufacturing had a major effect on nanoparticle shape. Chloroform produced the best spherical nanoparticles. Size and polydispersity were affected by surfactant concentration, stearic acid concentration, and homogenization amplitude.
Once optimized, the nanoparticles were successfully loaded with LL-37. The LL-37-loaded nanoparticles maintained their morphology and cytocompatibility (did not harm cells). They showed antibacterial activity against the reference strain of Streptococcus pyogenes (ATCC 12384).
Reczyńska-Kolman, Katarzyna; Ochońska, Dorota; Brzychczy-Włoch, Monika; Pamuła, Elżbieta · In Vitro
RPEP-12891 · 202575 antimicrobial peptides identified in one lizard species—far more diverse than expected—with consistent chromosomal organization across multiple species.
Otalora, Katherin; Gómez-Garrido, Jessica; Baldo, Laura · In Vitro
RPEP-12916 · 2025Five lipidated derivatives of KR12 (C10, C12, C14, 2-butyloctanoic acid, and 4-phenylbenzoic acid variants) showed strong antifungal activity against planktonic Candida cells, and C14-KR12-NH2 additionally disrupted Candida albicans biofilms—a notoriously drug-resistant state.
Paduszynska, Malgorzata Anna; Neubauer, Damian; Kamysz, Wojciech; Kamysz, Elzbieta · In Vitro