Circulating cathelicidin LL-37 in adult patients with pulmonary infectious diseases

Majewski, Karol; Żelechowska, Paulina; Brzezińska‐Błaszczyk, Ewa

doi:10.25011/cim.v40i1.28052

Cited by 20 publications

(16 citation statements)

References 26 publications

(35 reference statements)

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“…Moreover, elevated circulating LL-37 levels in adult patients with pulmonary tuberculosis, in comparison with healthy subjects, were noted [16]. In our previous studies, we also observed significantly higher concentrations of this peptide in the serum of adult patients with pulmonary tuberculosis [17]. Significantly elevated LL-37 levels in bronchoalveolar lavage (BAL) fluid of children with pulmonary tuberculosis were noted, as well [18].…”

Section: Discussionmentioning

confidence: 75%

Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections

Majewski¹,

Kozłowska²,

Żelechowska³

et al. 2018

cejoi

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Nowadays, data indicate that antimicrobial peptides play an important role in immunological defense. Human cathelicidin LL-37 possesses a broad spectrum of antimicrobial properties against Gram-positive and Gram-negative bacteria, and is thereby an important component of defense mechanisms within the respiratory tract. In this study, we determined the LL-37 serum level in patients with pneumonia caused by different bacteria species in comparison with healthy subjects. Twenty-two patients with pneumonia caused by coccal Gram-positive bacteria (I), 16 patients with pneumonia caused by Haemophilus influenzae (II), 29 patients with pneumonia caused by members of the Enterobacteriaceae (III), 13 patients caused by non-fermenting Gram-negative bacteria (IV), and 30 healthy controls were enrolled in the study. Serum LL-37 concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The mean LL-37 concentration in pneumonia patients was significantly higher in group I (p = 0.0032), group II (p = 0.0022), and group III (p = 0.019), and significantly lower in group IV (p = 0.000004) as compared with healthy volunteers. Our data suggest that LL-37 plays an important role in defense mechanisms during pneumonia. The reduced level of this peptide in subjects with pneumonia caused by opportunistic bacteria may reflect weakened immune system reactivity in these patients.

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Section: Discussionmentioning

confidence: 75%

Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections

Majewski¹,

Kozłowska²,

Żelechowska³

et al. 2018

cejoi

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“…In healthy individuals, the LL-37 levels were as low as 39.9 pg/mL in sputum [ 45 ], 1–4 ng/mL in tracheal aspirate samples obtained from new-born children [ 46 ], 30.5 ng/mL in saliva [ 47 ], and 1.1 and 1.7 ng/mL in plasma of neonatal and maternal blood, respectively [ 48 , 49 ]. Admittedly, in healthy adult individuals, the serum concentration of this peptide is within the range 1-2 ng/mL [ 50 , 51 ]; however, Jeng et al [ 52 ] noticed that LL-37 plasma level was about 27.2 ng/mL. Furthermore, concentrations of LL-37 in sweat and BAL of healthy infants are significantly higher and amount up to 4.47 μ g/mL [ 53 ] and 4.8 μ g/mL, respectively [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Cathelicidin LL-37 Affects Surface and Intracellular Toll-Like Receptor Expression in Tissue Mast Cells

Agier

Brzezińska‐Błaszczyk

Żelechowska

et al. 2018

Journal of Immunology Research

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Undoubtedly, mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, they release many proinflammatory and antimicrobial mediators, and they express pattern recognition receptors, such as TLRs. These receptors play a key role in recognition and binding molecules associated with microorganisms and molecules associated with damage. Cathelicidins exhibit direct antimicrobial activities against a broad spectrum of microbes by perturbing their cell membranes. Accumulating evidence suggests a role for these molecules in supporting cell activation. We examined the impact of human cathelicidin LL-37 on tissue mast cell TLR expression and distribution. Depending on context, we show that LL-37 stimulation resulted in minor to major effects on TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9 expression. Confocal microscopy analysis showed that, upon stimulation, TLRs may translocate from the cell interior to the surface and conversely. FPR2 and EGFR inhibitors reduced the increase in expression of selected receptors. We also established that LL-37 acts as a powerful inducer of CCL3 and ROS generation. These results showed that in response to LL-37, mast cells enhance the capability to detect invading pathogens by modulation of TLR expression in what may be involved FPR2 or EGFR molecules.

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“…Decreased LL-37 levels may be associated with the development of ILD. Majewski et al28 established that the mean level of LL-37 was significantly higher in patients with TB than in those with gram-positive bacteria-induced pneumonia, with gram-negative bacteria-induced pneumonia, and in healthy controls. Their observations clearly documented that cathelicidin LL-37 plays a role in defense mechanisms against infectious agents and is particularly important when the infection is caused by an intracellular pathogen.…”

Section: Discussionmentioning

confidence: 99%

<p>Evaluation of plasma antimicrobial peptide LL-37 and nuclear factor-kappaB levels in stable chronic obstructive pulmonary disease</p>

Uysal

Şimşek

Durmuş

et al. 2019

COPD

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BackgroundAntimicrobial peptides are effectors of host defence against infection and inflammation and can encourage wound repair.ObjectivesThe objectives of this study were to investigate the plasma antimicrobial peptide LL-37 and nuclear factor-kappaB (NF-κB) levels in patients with stable COPD compared with a control group and to highlight their importance in immune inflammation.MethodsOne hundred and thirty-eight stable COPD patients and 33 control subjects were enrolled in the study. The COPD patients were classified into four groups based on FEV1 (groups I–IV) and also divided into “low-risk and high-risk” groups (groups A–B [low risk], C–D [high risk]).ResultsPlasma LL-37 levels were significantly lower while plasma NF-κB levels of the COPD patients were significantly higher than those of the control subjects (P<0.001, both). LL-37 levels were significantly lower in group IV than in groups I, II, and III (P<0.01, all). NF-κB levels were significantly higher in groups III and IV than in groups I and II (P<0.05, both). There was a positive correlation between FEV1 and FEV1/FVC in all COPD patients (r=0.742, P<0.001) and in group D (r=0.741, P<0.001). Furthermore, there was an inverse correlation between LL-37 and NF-κB in both the groups C (r=−0.566, P<0.001) and D (r=−0.694, P<0.001) and group C+D combined (r=−0.593, P<0.001). Furthermore, in group C, LL-37 and FEV1 were positively correlated (r=0.633, P<0.001).ConclusionOur study indicated that plasma LL-37 and NF-κB may play an important role in chronic immune inflammation. Decreased LL-37 levels may be particularly high risk for patients in stage IV disease. The role of LL-37 as a target for treatment of the immune system and COPD must be widely evaluated.

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Circulating cathelicidin LL-37 in adult patients with pulmonary infectious diseases

Cited by 20 publications

References 26 publications

Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections

Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections

Cathelicidin LL-37 Affects Surface and Intracellular Toll-Like Receptor Expression in Tissue Mast Cells

<p>Evaluation of plasma antimicrobial peptide LL-37 and nuclear factor-kappaB levels in stable chronic obstructive pulmonary disease</p>

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