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Unlike the adaptive immunity that recruits T\u2010cells and specific antibodies against antigens, innate immune cells express pathogen recognition receptors (PRRs) that can detect various pathogen\u2010associated molecular patterns (PAMPs) released by invading pathogens. Microbial molecular patterns, such as lipopolysaccharide (LPS) from Gram\u2010negative bacteria, trigger signaling cascades in the host that result in the production of pro\u2010inflammatory cytokines. LPS stimulation produces a strong immune response and excessive LPS signaling leads to dysregulation of the immune response. However, dysregulated inflammatory response during wound healing often results in chronic non\u2010healing wounds that are difficult to control. In this work, we present data demonstrating partial neutralization of anionic LPS molecules using cationic branched polyethylenimine (BPEI). The anionic sites on the LPS molecules from <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) and <jats:italic>Klebsiella pneumoniae<\/jats:italic> (<jats:italic>K. pneumoniae<\/jats:italic>) are the lipid A moiety and BPEI binding create steric factors that hinder the binding of PRR signaling co\u2010factors. This reduces the production of pro\u2010inflammatory TNF\u2010\u03b1 cytokines. However, the anionic sites of <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (<jats:italic>P. aeruginosa<\/jats:italic>) LPS are in the O\u2010antigen region and subsequent BPEI binding slightly reduces TNF\u2010\u03b1 cytokine production. Fortunately, BPEI can reduce TNF\u2010\u03b1 cytokine expression in response to stimulation by intact <jats:italic>P. aeruginosa<\/jats:italic> bacterial cells and fungal zymosan PAMPs. Thus low\u2010molecular weight (600 Da) BPEI may be able to counter dysregulated inflammation in chronic wounds and promote successful repair following tissue injury.<\/jats:p>","DOI":"10.1002\/cmdc.202400011","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T22:20:31Z","timestamp":1715638831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low\u2010Molecular Weight Branched Polyethylenimine Reduces Cytokine Secretion from Human Immune System Monocytes Stimulated with Bacterial and Fungal PAMPs"],"prefix":"10.1002","volume":"19","author":[{"given":"Neda","family":"Heydarian","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Ferrell","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayesha S.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics Oklahoma State University  307 Life Sciences East Stillwater OK 74078 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chase","family":"Roedl","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongkai","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tra D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Best","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics Oklahoma State University  307 Life Sciences East Stillwater OK 74078 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-405X","authenticated-orcid":false,"given":"Charles V.","family":"Rice","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/147323000903700531"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027317"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13032535"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2014.0557"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.1057766"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2017.0761"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01058-16"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170710120556"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.13008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6978936"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-200306000-00009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00649"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13298-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.11.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines5040034"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","unstructured":"Patrick S. 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